>> Sandra Charles: Good morning.
And welcome to this our third
Cancer Moonshot Program.
I tell you, I said, "How am I
going to warm the [inaudible],"
because I thought you're going
to come in here, you know,
some people come running
on the stage to the music.
I won't do any of that.
But I do pledge to you
that when you leave here,
you will be much more informed,
better informed and feel
so edified, as well as fulfilled
that you now understand why all
of this focus on research,
why is it that we're spending
so many dollars in trying
to do these scientific
programs and research.
And the great thing is, this
being the third program,
we did the first one explaining
all about Cancer Moonshot,
because it was actually
fabulous the way it was timed,
because our program
occurred the day
after Congress passed the Cures
Act, which actually is going
to be funding this and many
other avenues of research.
So it was very timely.
And then last year we did the
Cancer Genomics Program showing
you how far we had come
with that research in terms
of precision medicine and moving
towards personalized medicine.
And so today we thought
we must keep this going.
And so we're doing
translational medicine.
Sounds nice and lofty, right?
And it's pretty much
it's been [inaudible]
to bench-to-bedside, basically.
And so it's the why
of all the research.
Why are we doing this?
Because at the end of the day
we could have a lot of papers
and a lot of findings, but
unless we can translate
that into something usable,
where we can help patients,
then it does not
quite meet its goal.
And the legacy of the
Apollo landing back
in 1969 was the coining
of the term "moonshot."
To speak to something that is
so audacious that it would aim
to do something that
seemed virtually impossible
and beyond the realm
of all possibility.
And so that alone gives
us a sense of hope.
Not trying to create vain
hope, but trying to have people
to understand that all this
complex science can be distilled
into something very useable.
And that is why in our
program today we have not only
clinicians, but also
our experts, scientists
and researchers, and
our patient advocates.
So I think you're
in for a real treat.
And I would like to ask my
colleague, Dr. Mary Mazanec,
the director of the
Congressional Research Services
to come and welcome
you to this program,
and prepare you to
hear our speakers.
So thank you so very much.
[ Applause ]
>> Mary Mazanec: Thank
you, Dr. Charles.
So I am -- I think I
just broke the mic here.
What a way to start.
I'm very excited to be
here with you today.
And it is my pleasure to
welcome all of our guests here
to the Library of Congress.
As Dr. Charles noted, this
is the third in a series
of discussions centered on the
Cancer Moonshot Initiative.
The Cancer Moonshot Initiative
was initially authorized
in the 2016 Cures Act.
And the ultimate goal of this
critical initiative is really
to identify and develop
new therapeutics
to diagnose and treat cancer.
Now, despite all the
advances in medical science,
cancer remains one
of those diseases
that still poses a major health
threat to so many Americans.
I think it's fairly
accurate to say
that cancer affects
virtually everybody.
Many of you probably know
someone whose life was forever
changed when they received a
diagnosis of cancer, or you,
yourself, may have had your life
turned inside out and upside
down when you received
a cancer diagnosis.
As some of you know, I'm a
physician, I'm a pulmonologist,
and before I came to D.C.
when I was seeing patients,
I took care of many
patients who had lung cancer.
And lung cancer back then
was pretty much a diagnosis
that ultimately resulted
in death.
But I saw firsthand the pain and
suffering that my patients went
through after the diagnosis
through the various
courses of therapy.
As some of you probably
appreciate,
cancer is the second
leading cause of death,
both in the United
States and worldwide.
And then, although
scientific breakthroughs,
some of which you
have witnessed,
I witnessed over the
last several decades,
have actually improved the
diagnosis and the survival rates
of individuals with cancer.
There's so much more to be done.
And we're not there yet
in declaring victory
over all types of cancer.
So recognizing this,
President Obama, basically,
tasked the former vice
president, Joe Biden,
who had just lost his
son to brain cancer,
to lead a new national
initiative termed the
Cancer Moonshot.
Congress has been on board
from the very beginning,
and has led the charge
towards conquering cancer
by consistently working
in a bipartisan manner.
This is one of the areas
where I think there is
bipartisan agreement.
And they have grappled
with numerous policy issues
in the area of science,
technology and medical research.
But, as we all know,
advancements are costly.
There's a price tag associated
with medical research.
And Congress has been
aggressively funding research
in the areas of medical
science that are needed
to precipitate clinical
progress.
So, just for example,
in fiscal year 2019,
the appropriations
included 5.74 billion
to the National Cancer
Institute,
which was a $79 million increase
over the previous fiscal
year to fund research.
As Dr. Charles said, this is the
third in the series of seminars
that she has organized focused
on the Cancer Moonshot
Initiative.
The first one was done shortly
after the bill was passed,
and brought together
scientists, healthcare providers
and patients in a
dialogue surrounding this
major initiative.
The library hosted its second
seminar in October 2017.
And I had the opportunity to
participate in that one also.
The topic of that one
was cancer genomics.
Cancer genomics dictate how
a tumor behaves, and whether
or not it responds to treatment.
As many of you realize,
the mapping of the human
genome was a major step forward
in biomedical research, and
it really opened the door
to a whole new area of
research and approach
to treating many
diseases, including cancer.
It also heralded the
dawning of personalized
or precision medicine, where
treatments are actually targeted
or individualized
to a given patient.
So recent genetic breakthroughs
have actually expanded our
understanding of cancer.
And this has resulted in new
ways to diagnose cancer and,
hopefully, pick it up early on
in the course of the disease
when it's still very
treatable and curable.
And it has also precipitated
this paradigm shift away
from traditional therapeutics
to more newer approaches,
many of which use
one's own immune system
to target cancer cells.
Now, today we're going to hear
from a very distinguished panel
of experts, and from
the individuals
that are patient advocates
who have actually
experienced cancer themselves,
to probe more deeply into this
area of research, which is,
basically, based on a
translational medicine approach.
Now, as Dr. Charles explained,
translational medicine seeks
to improve the health and
wellbeing of patients by,
basically, connecting the
dots between what's happening
in the laboratory at the
bench with basic research
to the clinical practice
of medicine.
Now, in a former life
before I came to Washington,
I actually spent
quite a few hours
at the bench doing research.
And my hope was that at some
point what I was doing would
have an impact on patient care,
and would improve the
lives of individuals.
So this whole area
of translational medicine
is a major interest of mine
that I've followed over the
years here in Washington.
As I said, it's been described
as a bench-to-bedside approach
where discoveries in the
laboratory are leveraged
and "translated" or
developed into new therapies.
But in order for this to happen,
you have to the scientists
actually doing the work,
speaking to, collaborating
and sharing information
with clinicians and
medical care providers
who are actually
taking care of patients.
And this is what the Cancer
Moonshot is intended to do.
And I'm going to quote
Vice President Joe Biden
who explained the purpose
of the Cancer Moonshot
Initiative with these words.
"The Cancer Moonshot Initiative
is to better understand
and breakdown the
silos and stovepipes
that prevent the sharing of
information and impedes advances
in cancer research
and treatment,
while building a focused
and coordinated effort
at home and abroad."
So, in this sense, translational
medicine is a tool.
It's an approach that is
central to the success
of this major initiative.
It has both the power and
the potential to be the force
that drives us towards,
ultimately,
crossing the goal line in
finding a cure for cancer.
The National Cancer
Institute has a lead
and a central role
in this effort.
They actually have a program
called the Transitional Research
Program at NCI.
And this program sponsors
grants in research excellence
that actually tries to
promote the collaboration
between clinicians
and basic scientists
to discover new approaches to
attack diseases such as cancer.
So I think I've spoken enough,
or I've taken up too much
of the time already,
because I really want to hear
from our distinguished
panel of experts.
They are going to share their
various perspectives with us.
And we are joined
today by Dr. John Tsang
from the National Institutes
of Health, who is an expert
on human immunology
and systems biology.
We also have Professor
Elizabeth Platz
from John Hopkins University,
the School of Public Health,
who is a leading
cancer epidemiologist.
We also are joined
by Dr. Susan Bates
from Columbia University Medical
School, who is a clinician
and a cancer epidemiologist.
And we have two patient
advocates, Ms. Juanita Lyle
and John Bauer, who are also
cancer survivors themselves.
So I'm going to turn the
program over to them.
And, again, welcome.
[ Applause ]
>> Tomoko Steen:
Welcome, everyone.
This event was co-sponsored
with the Science, Technology
and Business Division.
You can see this, we
organized [inaudible] lectures.
And you can see videocasting,
this page.
And also we had two previous
Cancer Moonshot videos
are there.
And also we invited several
Nobel laureate to talk
about translational medicine.
And that video is there as well.
So I hope you enjoy it.
Okay. I can't fix this.
Okay. I'm Tomoko Steen at
the Science, Technology
and Business Division.
It's my pleasure to
introduce our speakers.
And the first speaker
is Dr. John Tsang.
And he is at the National
Institute of Allergy
and Infectious Diseases.
He leads a project,
and is also co-director
of the NIH Center
for Human Immunology.
And Dr. Tsang has training
in computer engineering
and computer science, and also
a biophysics Ph.D. from Harvard.
So he has received many prizes
from the National
Institute of Health.
And one of the highlights of his
program is OMiCC, and he's going
to talk about that in his talk.
[ Inaudible Speaker ]
Thank you.
[ Applause ]
>> John Tsang: Good morning.
Good morning.
Thanks for having me here.
It's an honor to speak.
So, as Dr. Steen mentioned, I
work on the human immune system.
So today I'm going to tell
you a bit of my perspective
and highlighting the
feel of immunotherapy.
And so the title of my talk is
"Towards personalized
immunotherapies: Predicting
and understanding the immune
responsiveness of individuals."
So I don't think I
need to convince you
that the immune system
is very important.
And it's been implicating
a large number of diseases.
So, therefore, understanding
and knowing how it
works is very important.
So, aside from infection
and autoimmunity,
[inaudible] you may of heard of,
the immune system has been
implicated in, for example,
metabolic issues, for
example, obesity, diabetes,
also neurological disorders.
So you name any disease, you
can always find a connection
to the immune system.
And, of course, cancer, being
such a devastating disease,
it's a huge connection
to the immune system.
So you may have heard that
most recently the Nobel Prize
in medicine was awarded
to two immunologists
for their discovery of cancer
therapies by inhibition
of negative immune regulation.
Right? So today I'm going
to give you an overview
of the science behind this,
and also that sort of leads
into my perspective
on how we need
to move towards a more
personalized approach
to immunotherapy.
So the immune system, broadly
speaking, it looks for,
basically, dangerous signs
and signals and attacks.
So here's a video showing if you
induce damage at a tissue site,
you can see immediately the
red, those are neutrophils,
a type of immune cell, they
would immediately sense
that damage, and come
and swarm that site,
and then try to repair
the damage.
Right? So that's one example.
And then the green ones,
they are another immune cell
type called macrophages.
So there they're interacting
with the neutrophils
in this case to perform
the repair.
So, in general, there's a
type of cell called T cells.
It's a type of immune cells
that they are the
soldiers, basically.
You can think of the
soldiers of the immune system.
They can remember and also
recognize harmful things
such as pathogens and tumors.
So these T cells
would look for things
that are harmful in your body.
They circulate around
and patrol.
Right? And then they scan
for cells, and then they try
to distinguish between
normal and abnormal cells.
So these abnormal
cells, typically,
sometimes they raise a flag,
and they will just
display certain patterns
that the immune system
can sort of tell, "Oh,
this is likely some cell
that's either infected,
or it has some aberration
inside the cell."
And then once it's detected
that potentially harmful cell,
the T cells would try to
destroy those cells, basically.
Right? So here's a very basic
picture on how T cells work.
On the left is what we
call a cytotoxic T cell.
So these are the cells
that can kill these harmful
or dangerous cells.
And on the right is a tumor cell
or a viral infected
cell, for example.
So these are dangerous
to our body.
So these cells, they can
present or they can show
up on their surface
something called an antigen.
So that's, basically, a
signal for the immune system.
The antigen is something that
the immune system can recognize
as "Oh, this is foreign,"
for example, to the body,
or "This is something that
the body shouldn't have."
Therefore, the cytotoxic T
cells would recognize that,
and then start to interact
with these cells, and,
eventually, trying
to destroy it.
So that's the very basics of
how cytotoxic T cells work.
Right? So how does
the immune system find
and kill tumor cells?
Right? So the very first
step, it's the tumor cells,
they have to display
these signs and antigens.
Right? So that's
the very first step.
Basically, this is going from
-- the tumor cells would die,
for example, and then they would
release these kinds of antigens.
So that would allow the
immune system to start to pick
up these signs, and start
presenting them to the T cells
that I was talking about.
So now these T cells, they're,
like, in training, basically.
So they can be trained now
to recognize these antigens
or signals from these
tumor cells.
So once these cells are
trained, the step three,
it's called priming
and activation.
So what the the green guy,
right, this green guy is,
basically, kind of
like a messenger.
They pick up these signals
from these dead cells,
and then they start to go
and talk to their colleagues,
in this case, the T cells.
Right? So the T cells
are the soldiers.
So then these soldiers are now
trained by the green guy now.
Right? So now they
become activated soldiers.
They now know what to look for,
because the green guys
convey the information
about these antigens
to these soldiers.
So now these soldiers are
walking through, basically.
In this case, going through the
bloodstream, searching for cells
that are displaying
those signals, basically.
Right? So then they
enter the tumor.
They have to cross multiple
bridges before they can get
into the tumor.
You can see these bad guys.
Those are the tumor
cells, the red guys.
Right? So these soldiers
are now going in,
and then they would
recognize them based
on the principles I
mentioned earlier.
And then they can kill
these cells, basically.
And this is a fairly specific
process, as you can imagine,
right, because these
cells are not just looking
for some random cells,
because they are instructed
by the step one, basically.
When antigens are released from
these sort of tumor cells dying,
or they're not so happy, they
are releasing these things
into the environment,
get picked up, basically.
So this is a very
fairly specific process.
So this is precisely why
this holds a lot of promise,
because the person's
immune system can adapt
to the tumor characteristics
that's fairly unique
to that individual.
Right? So that's the key here.
So when you think about cancer,
it's really not a
single disease,
even within an individual.
So here's an example of
sort of a conceptual picture
of what really is in a tumor.
So going from left
to right, it's time.
So, initially, you may
have some clones of cells
that somehow something
went wrong inside of them,
and they keep dividing.
Right? So that's the
basis of a tumor.
But as it goes through over
time, these things start
to mutate, meaning they are
changing their genetic material
and instructions.
And then some of the changes
would allow them to proliferate
or rapidly divide even faster.
Right? So now you have
different clones, as indicated
by the different
colors of cells.
So over time, you have
lots of, basically,
different tumors in your body.
And so in the case of more
classical non-immune therapies,
even very specific
targeted therapies,
they may be targeting a
subset of these clones,
but as the tumor evolves over
time, it's actually very hard
for these drugs to kill
all the different clones
within the tumor.
So that's where the immune
system is really holding a lot
of promise, because
T and B cells,
they have enormous
diversity, so they're the kind
of cells I just told you about.
Right? They're not static.
They're not fixed.
They're learning all the
time about what's going on.
And they have a lot
of diversity.
So they're like a personal
targeted drug factory.
So you don't need to
instruct it to what to do.
If it sees some harmful things
in the body, it starts to react
to it, and then clone
themselves.
In a way it's like your
anti-tumor clone army.
Right? It's like cloning
itself making sure
that it has enough numbers
to destroy the tumors.
And it's massive.
And this is actually
very fascinating biology.
If you look into a T cell, also
a B cell if it's another type
of immune cell, they're the
only cell that's in your body
where there's parts of the
DNA that can be rearranged.
So they can rearrange
in a fairly random way
to generate lots of diversity.
So they can, basically,
recognize almost anything,
be it in the pathogen
or in the tumor.
Right? So that's what gives
them a lot of the ability
to recognize all sorts of
mutations in your tumors.
So, well, is that it?
I mean, that's great.
We have this system.
Right? It could kill
these tumors.
But there are actually
many inhibitory factors
that actually make it
impossible for the T cell
to kill the cancer cells also.
And when you really
think about it,
that's because the immune system
also needs to be regulated,
right, because that's,
for example,
why we have autoimmunity.
Right? So you cannot just let
these T cells to go out there
and just replicate indefinitely
once they see some antigens,
and start to kill lots of
cells, because you still need
to pull it back also
at the same kind.
So that's called resolution.
So that's why the immune
system has evolved ways
to regulate these
cells at the same time.
But those regulations,
of course,
can be taken advantage
by tumors.
So the tumors are not stupid.
Right? They are pretty
smart as well.
They also evolve.
So that's exactly what Jim
Allison and Dr. Hangzhou
and others in the
field have discovered.
It's a way to inhibit these
kinds of negative regulation
to then allow to, basically,
release the brake,
to allow the T cells.
So in this particular
case, on the left here,
you can see the T cells that
I mentioned in the blue,
and then the other
one is the tumor cell.
So the tumor cell in this
case has evolved a way
to display a signal
on their cell surface
to tell the T cell
to stop, basically.
So the T cell would then go,
basically, idle once it sees
that signal, because that's
the negative regulatory signal.
Right? So Jim and Dr. Hangzhou,
what they did is they figured
out ways to block those signals
so that the tumor can no
longer instruct the T cell
to stop, basically.
So, therefore, the T cell
can now become more active
and kill these tumors.
But despite that advance,
if you look at the response
to immunotherapy, so
here's what's called a
Kaplan-Meier plot.
So on the x it's time over time.
So you, basically, enroll
a group of patients,
give them the therapy, and then
on the x it's the
percent of survival.
So here there are two curves.
On the red it's looking
at a [inaudible] immunotherapy
called anti-CTLA-4.
So that's the approach that
Dr. Jim Allison discovered.
So in this case you can
see that over time a lot
of the patients actually
don't respond, as you can see.
And they approach a steady state
of about 25% survival,
basically.
And that seems to be a
fairly constant number.
So if you now look at
these trials, typically,
about 25% of the
patients actually respond
to that therapy.
The rest don't respond
to that therapy.
Yes, by the way, these are
metastatic melanoma patients,
a fairly aggressive
form of cancer.
On the blue here, it's showing
you some recent advances
where they combined
multiple immunotherapies.
And that has done really
well, as you can see here
in this particular
type of cancer.
It gets to about a
60% response rate.
Right? But still, a good
35-40% of the patients,
they don't respond at
all to that therapy.
So the question is why.
Right? So what factors may
predict and, potentially,
determine whether a person will
respond to that therapy or not?
Right? So that's one
of the major questions.
So there's some known
indicators of responsiveness.
For example, whether there's any
T cells at all in these tumors.
Right? So that's a major factor.
There are tumors that
there are no T cells.
Basically, it's like a desert.
And then we're still figuring --
I mean, the few are
still figuring
out why that's the case.
And also there may be T cells
that they may be blocked
from entering into the
relevant sites in the tumor.
So there are images showing,
for example, T cells, basically,
they're fairly active,
but they're all
in the periphery of the tumor.
They just couldn't get in.
The other factor is whether
the tumor is hot or cold.
I mean, there may be T cells,
and there may be the tumor,
they may be interacting,
but there may not
be enough signals
[inaudible] inflammation.
So, basically, the immune system
relies on inflammatory signals
for it to act, basically.
So there may not be enough
signal to tell the T cells to,
"Ha, activate yourself
and kill these tumors."
Right? So these are all
found in different patients.
So one patient may
not have the T cells.
Another may have the T cells,
but the T cells may not be able
to enter the tumor, or they may
all be interacting, mixing up,
but there's not enough
external signals
to instruct the T
cells to go in.
And the other factor
is also, of course,
going back to the picture
I showed you earlier,
are these tumors hiding the
fact that they're tumors,
or are they actually
presenting these antigens,
or are they making antigens for
the immune system to be trained.
Right? So that's
another key factor.
But there's much
remaining to be discovered.
There's many different types
of tumors, as you can imagine.
I just showed you an
example on melanoma.
And there's many
different types of patients,
and many different
activation thresholds.
The immune system, at the end
of the day, is very complex.
Right? So you may want to
now go to your doc and ask,
"How's my immune system?
Is it good enough to fight
off a tumor, for example?"
Right? Unfortunately, right now
we actually don't have a lot
of ways to tell patients how
well our immune system is doing.
I mean, typically, you can get
what's called a complete blood
count so you can get
the frequency and level
of different immune
cells circulating
in your body, for example.
That's quite informative,
like, for example,
to tell whether you have
an infection or not.
But it's far from
sufficient to give you a sense
of how well the immune
system is working,
or how responsive the
immune system would be
if it encounters some
danger or harmful signal.
Right?
So that sort of leads to
my perspective on the need
to measure the immune
and then tumor status
in the human population.
So the immune system is
quite unique in the sense
that it's a system in
your body that is far
from completely dictated or
specified by genetics alone.
So early when one is a baby,
a lot of that may be
specified by genetics.
But actually over time, because
of the environment and exposure,
there's accumulating evidence
suggesting that the state
of the immune system is
far from just explaining
that by genetics alone.
So you need to know a lot
more about the immune system
than just knowing
somebody's genome, basically.
So, fortunately these days,
there's rapid advances
in technology.
So, for example, you can
now go into immune cells,
and look at the activity
of the genes.
You can now do what's called
sequencing, which is also used
to look at the human genome.
But you can now use to look
at the immune cell diversity,
like different T
cells and B cells.
And you can also, of course,
look at genetic changes
in tumors at the same time
within that individual.
There are a lot of
fancy machines
that can now really look at the
properties of the immune cells
in a fairly high
throughput manner.
Right? So now from a drop
of blood from a patient,
you can actually generate tens
and thousands of data points,
potentially informative
of our immune system.
So this now then becomes more
of a data science problem.
Right? So you have lots of
data points per individual,
and you have lots of different
individuals with different types
of tumors, and different health
and statuses, for example.
So this is where the machine
learning aspect would come
in to help us to find
markers of responsiveness.
Right? So you start
off, as I mentioned,
you have the immune
measurements of an individual
in a large population, so
these various characteristics,
including the ones
I mentioned already.
And now the question you want
to ask is actually what feature
out of your tens and thousands
of data points may help
you predict whether
that particular individual,
right, will respond well or not,
or how they will respond,
or how the individual
actually will respond
to a particular type
of immune therapy.
So there are rapid advances in
[inaudible] of machine learning
and computer science,
where these techniques are
now fairly applicable due
to this kind of problem.
And so one example, which is
coming from work in my lab
in the Center for Human
Immunology at the NIH,
where we're asking
a similar question,
but in the context of vaccines.
And it turns out that when
somebody gets vaccinated to,
for example, the seasonal flu,
our responses can
be very different.
So some individuals may
not respond at all in terms
of antibodies, which are
the mediators of protection.
Some individuals may not
have a gigantic response.
But what makes one person
respond much better compared
to another?
Right? So we did a study where
we kind of took the approach,
I told you, we generated lots of
data points for each individual,
and then asked the question
whether we can find some sort
of set point or baseline,
meaning before the individual
even got the vaccine,
then we used their
immune statuses
to predict how well they
respond to the vaccine.
Right? So on the right here is a
cartoon showing you may have hot
individuals, they respond well.
While the colder ones, they
may not respond as much.
Right? So what we found is
what we call a signature
or a predictive signal in these
individuals that we were able
to replicate, in this case,
across different populations
of people who got the
vaccine, so in this case.
So I'm just showing you sort
of a summary of the result
without going into the
details, on why it's sort
of like the immune
responsiveness score.
Right? So that's what you
want to compute in a way
for your patients,
also cancer patients,
when you give a [inaudible]
immunotherapy,
you want to find a
way to combine data
from multiple modalities,
be it cells or genes
or gene activities,
derive such a score,
and that score should
allow you to delineate.
So in this particular example,
I'm showing you the
low responders
versus the high responders
to a vaccine.
But you can imagine a good
versus a bad responder
to immunotherapy as well, right,
such that you can now see
this had to work, be applied
and applicable across
different populations.
So in this case across different
seasons of vaccination.
And this is I'm showing
you also on the right,
it's even extendable to look
at different types of vaccines.
So in this case, yellow fever
is another type of vaccine.
Right? So this is sort of
an example showing sort
of the applicability and
potential extensibility
of such signatures to be
applied to the broad population,
but also to different
types of interventions.
So moving forward,
my perspective is
that we require two kinds
of science to build the kind
of framework and to
push things forward.
One is citizen, and the other
one is team science, basically.
So as you can imagine
to generate the kind
of data I mentioned
that requires a lot
of patient participation, right,
to help with the data
generation, we need to look
at different tumors,
we need to look
at different personal
characteristics, we need to look
at different immunotherapies,
and we need to look
at the very diverse
immune system statuses
that I mentioned.
The other is team science.
It's becoming complex,
these problems.
So it's not simply collecting
data from five patients,
and look at them in
the lab for six months,
and then publish a paper.
But rather that we need
to collect these data,
and you need a lot
of collaboration
among the clinicians
and computational
biologists, immunologists,
software engineers to build
a software infrastructure,
and also a lot of technology
that's needed to advance
to make these the sort
of measurement technologies
I mentioned.
Right? They are working well
in the lab, but to push those
into the clinic, and
make them relevant,
and make them cost-effective,
there's still some way to go.
So with that I just want to wrap
up, give you sort of a vignette.
It's a mix of citizen
and team science.
So the traditional way that
scientists do their science is,
typically, we generate a
hypothesis, we may say that,
"Well, I hypothesized
that neutral fields
of a particular type of
immune cell may be able
to kill a particular
type of tumor."
So that's a hypothesis
I just made.
It may not be true.
So, well, then what I do is I
go out and I think about it,
and then I design an experiment,
and see if I can start slowly
making progress to either prove
or disprove the hypothesis
I just made.
Right? And then you generate
data to test the hypothesis.
This goes in cycles.
So that's how science
is, typically, done.
So what I would like to propose
is a slightly revised paradigm,
given the kind of data that we
have already made available now
in the public domain actually.
So NIH sponsors a lot
of large-scale data
generation projects that some
of these data you can
download them actually.
So instead of jumping right
in to design a new experiment,
you could think about
generate your hypothesis,
and utilize these existing data
as much as possible, right,
to explore and then refine your
hypothesis before you go again,
and go back to the
traditional paradigm
with designing your experiment,
then go back and do this again.
But to enable this,
you need tools.
So that's where this sort of
evolved out of our project
in the lab, because we have a
mix of computational biologists
in the lab, but also bench
experimental biologists.
The bench folks, they
are always envied
of the computational
folks who can just kind
of wrangle the data off the web,
and start generating
some new hypotheses.
So they started asking
me, "Can we do better?
Can we have some tools that
allow us to do this faster?"
So we ended up having
something internal development,
and then eventually we
decided this is useful
for the general public and
for the scientific community,
so we released it.
So this provides readily usable,
in this case, gene
expression data.
It's a type of genetic data
that's fairly widely available.
And there's lots of them.
So you can look at the activity
of genes, and different cells
and different tissues
and different people.
And you don't have to do
any programming or wrangle
with the data in this case.
It's all done for you already.
So what you can do is, by
point-and-click, you can say,
"I want to compare, let's
say, melanoma patients,
the blood gene expression
profile of those patients,
versus healthy people.
I also want to look at
lung cancer patients.
I want to look at
breast cancer patients.
And now I also want to combine
them all together, and ask,
'Are there any common things
that I can find across all
of those different datasets?'"
So that you can all do
within this platform.
And the other thing
that it allows you
to do is what I call
citizen science.
It allows you to share all the
metadata and the annotations.
All of those are done in
what I call a structured way,
meaning they're not just
free text, they're structured
in a way that's reusable.
Right? So now others can come in
and look at what you have built
in terms of, let's say,
the one I just mentioned
about tumor comparison.
So now you want to say, "Well,
I want to compare these
tumor data to infection."
That you can do.
I mean, if that's your question.
You can now get grab
some infection data,
and now combine them with the
tumor data that's already built
by another person, and put
them together, and ask,
"What are the differences,
what are the similarities,"
basically.
So that's the idea.
So we actually experimented
with this idea
to see whether it could
work with a group of people
with no prior training in
computational biology at all.
So we, basically, just sent
out an email to a mailing list
at the NIH, and told them that
there's an opportunity for you
to learn how to deal with a lot
of the large-scale
public datasets.
In return, can you
come here for a day?
You can learn about the tool,
but at the same time we're going
to give you a topic of research,
and we'll see what you can
do in a day, basically.
So we call this the
OMiCC Jamboree.
So they came.
And most of them
stayed for eight hours,
because we gave free
lunch and lots of donuts.
So about 29 of them came from
13 different institutions.
Right? So we divided them into
ten groups, asking them to look
at human autoimmunity.
Right?
So we happened to look at five
different autoimmune diseases,
in this case, in both human
and also mouse models.
Right? So in a day
they collected
over a hundred [inaudible]
versus healthy comparisons.
And you can ignore some of
the details in the table.
They gathered more
than a thousand,
basically, samples and datasets.
And then when we sort of
quality control them later,
look at them, about 75% of
them were really well formed.
So in a way you gather 29
people for eight hours,
so that's like about 230
FTE hours in the day.
They got a lot out of it.
They felt like they
learned quite a bit.
At the same time we actually
got something out of it, too,
because from the research we
almost answered a question
that generated quite a bit of
hypotheses about these diseases,
especially what were common
across the five model
diseases we looked at.
Right? So you're welcome
to look at a website.
We have a website
for this as well.
And you can sort of look at the
details if you're interested.
So I borrowed lots
of images on the web
to make this presentation.
So these are some
additional image credits
for the pictures I've shown you.
And then with that, I would like
to thank you for your attention
and the folks in my lab.
Thank you.
[ Applause ]
>> Tomoko Steen: We
take the questions
at the end of the speech.
Sorry. Thank you.
The next speaker is my dear
friend, Dr. Elizabeth Platz.
She's a professor at Johns
Hopkins Bloomberg School
of Public Health.
And she has a joint appointment
with the Department of Oncology
and also Urology at Johns
Hopkins Medical School.
And she received her doctorate
in epidemiology from Harvard.
And also has done a postdoctoral
research at Harvard as well.
That's where I met her.
And she has been
working on molecular
and genetic epidemiology.
And she's focused in
translational findings
to practicing and
preventing cancer,
especially her area
is prostate cancer.
[ Applause ]
>> Elizabeth Platz: All right.
Let me see if I can
get the next slide up.
That's all right.
[inaudible] do it.
Okay. So thanks so much
for having me here today,
Tomoko and your colleagues here
at the Library of Congress.
So I am a translational
researcher.
I'm a population scientist and
epidemiologist by training.
And I spend a lot of my time
collaborating with investigators
from other disciplines,
whether it's on prostate cancer
or other types of cancer.
So I should indicate
I have no disclosures.
So today I'm going to talk a
little bit about what we've done
to discover cancer
risk, protective
and prognostic factors.
So these are all
translational opportunities.
So all that we do is
multidisciplinary.
We collaborate, we
come together.
The areas I'm going to cover
today are opportunities
for cancer prevention, so drugs
used for other indications,
and whether or not they're
related to prostate cancer risk.
So I'll cover a few common drugs
for cardiovascular indications.
I'll also talk a little bit
about periodontal
disease and cancer risk.
And then, finally, I'll
talk about opportunities
for improving prostate
cancer prognostication
by using a biomarker
telomere length
and variability in
telomere length.
So here are the disciplines
that we tend to collaborate
with for our prostate
cancer research.
You can see there are
clinical disciplines,
there are basic science
disciplines,
there are very focused
disciplines like pharmacology,
and then my discipline,
epidemiology,
as well as biostatistics.
And we all come together to try
to solve the problem
of prostate cancer.
You saw an iterative
process like this
on one of John's slides.
So in our field we do
exactly what he said.
We test our hypotheses.
Our basic scientists are really
great at developing, testing
and discovering fundamental
pathways that are integral
to the development and
progression of cancer.
But the question that they often
pose is what's the relevance
of what they found
for human disease.
So they'll come to
me and they'll say,
"Can you study this
discovery within people,
within populations, populations
of people at risk for cancer,
populations of individuals
with cancer?"
So we then test these
hypotheses.
And then sometimes we
have interesting findings
that may be different from
what was hypothesized.
So the iterative process is then
to go back into the laboratory
to try to discover
mechanisms underlying,
and then come forward again.
And then eventually, when we
have what we think is an answer,
and when we can confirm it,
not just through basic science
and one epidemiologic study,
but maybe several epidemiologic
studies, we may feel confident
that we have an association
that may be causal
and could be acted on.
So here's the first example
that I want to share with you.
So this was a collaboration
across all those disciplines
that I showed you
including pharmacology.
What we wanted to do
was something called
drug repositioning.
We want to be able to identify
drugs for other indications
that may be helpful
for the prevention
or treatment of prostate cancer.
So I have a couple of my
colleagues shown here,
Bill Nelson, who's our
Cancer Center director,
and Vasan Yegnasubramaniun,
who's a cancer biologist
at the Cancer Center.
So, again, the goal was to
identify drugs that are used
for other indications that may
be helpful in the prevention
or treatment of prostate cancer.
And this approach is
called drug repositioning.
So what we did was we used
a multistage strategy.
So we started in the laboratory
performing a drug screen.
So our institution has a library
that has over 3,000 compounds
in it, almost 2,000
are FDA-approved drugs.
So in the first screen they
used two different cell lines,
prostate cancer cell lines,
and they looked for those drugs
that seem to be cytotoxic.
That is, they reduce the
proliferation of those cells,
reduce the multiplication
of those cells.
And based on that
screen, those that showed
at least a 50% inhibition
of proliferation,
they moved on to the
secondary screen,
which included many more
prostate cancer cell lines,
both androgen-independent
and dependent cell lines.
And then based on the top
hits, we then identified those
that we thought had the
greatest cytotoxic potency.
That is, the lowest
concentration,
the greatest inhibition,
and also were drugs
that were commonly used in the
U.S. so that we'd have a chance
to be able to study
them in the context
of a prospective cohort study.
And that was stage two.
So when we scanned through all
the drugs, we noticed that many
that came up were
antineoplastic.
So that is, they're already
used for chemotherapy.
So those are not the drugs we
wanted to be able to study.
So then we looked for
those that were not known
to be chemotherapeutic agents.
And actually the
top one that popped
up was disulfiram, Antabuse.
We weren't able to
study that one
within our prospective
cohort study.
But the second one that
popped up was digoxin.
Digoxin is an old drug.
It's used to treat
congestive heart failure
and also certain arrhythmias.
Again, it's an old drug.
It's not used very
much these days.
It is a sodium potassium
ATPase inhibitor.
What we noticed was there
was a second drug that popped
up that acted on
the same pathway.
And then among those that were
not FDA-approved there was
another that ranked fairly high.
And so we thought, "We can
study digoxin within one
of our prospective
cohort studies."
It was a common enough drug
used in older adults, again,
for the two indications
that I mentioned.
We were excited by that.
But then, as we looked through
the list of the top hits,
we also noticed that
there was another class
of drugs that popped up.
And these are the statin drugs.
So these are
cholesterol-lowering drugs,
very commonly prescribed in
the U.S. And this made us think
that our approach might
have some reasonableness,
because we had previously
studied statin drugs based
on their actions for fatal
and advanced prostate cancer,
and found that men
who took these drugs,
especially for a longer
term had a much lower risk
of developing advanced, meaning
metastatic prostate cancer,
or dying of their
prostate cancer.
I mean, a substantially
lower risk.
And this was taking into
account other known risk factors
for prostate cancer, as
well as other cardiovascular
and other commonly
used medications.
So we thought this
approach had some legitimacy
from a scientific perspective.
So then we looked at
our top hits, so, again,
digoxin and related drugs.
We found that men who tended
to use these drugs had
about a 25% lower risk of
developing prostate cancer.
And this was true including
for more aggressive disease.
And then if we looked
at the duration of use,
men who used the drug longer
tended to have a lower risk
of prostate cancer, whether
that disease was organ-confined,
localized to the prostate,
or the disease was
advanced or lethal.
So metastatic or caused death.
So we thought this was a
very exciting approach.
It was two-staged.
It was clearly
multidisciplinary.
We think this approach
actually helps reduce false
positive hits.
So if we had just taken the
drug screen and left it at that
and picked a few, we wouldn't
have known whether or not
that was just a false positive.
They had more than 3,000
drugs in that screen.
But by doing this two-staged
we reduced the likelihood
of false positive hits.
So we thought that
was super exciting.
This was the cover
of the article.
And this is to remind me
that the drug is derived
from the foxglove.
So it's a beautiful plant
that grows out in the west.
Okay? So we think this is
a super exciting approach.
And then just to tell you,
statin drugs continue
to hold up.
So as our colleagues have
looked, as we've looked
in our other cohort
studies, we continue to find
that statin drugs tend to be
associated with a lower risk,
especially of fatal
prostate cancer.
So in that cohort that
I showed you before,
that was the Health
Professionals Follow-Up Study.
We also continue to see
it in the ARIC Cohort,
which is a cardiovascular
cohort, the Atherosclerosis Risk
in Communities Cohort study.
And I show the first
author's photo here.
You can see that she's
a young investigator.
And so we're very proud of her.
This paper just came
out this week.
And here are the results.
So she sees an inverse
association
for fatal prostate cancer
for both users of fewer
than ten years, as well as
users for more than ten years.
And then for total
prostate cancer,
and this has not
been seen before,
because most cohorts don't
have this much follow-up time
to be able to look at very long
use, those who used the drug
for more than ten years also
had an inverse at a lower risk
of total prostate cancer.
And, again, this is taking into
account the number of factors
that are correlated with
both statin drug use
and prostate cancer.
So another drug, it's a very
commonly used drug, aspirin,
for cardio protective reasons,
as well as for pain reduction
and reduction in
inflammation as well.
So it's been well recognized
for a couple of decades
that aspirin use
seems to be associated
with a slightly reduced risk
of developing prostate cancer.
But there's not much work
on whether it's associated
with a lower risk of
fatal prostate cancer, or,
in men with prostate cancer,
whether it's associated
with a lower risk of dying
of their prostate cancer.
So this is work done by
another young investigator,
Lauren Hurwitz, who's now
a cancer prevention fellow
at the National Cancer
Institute.
And what she found
was that, indeed,
men who are regular aspirin
users have a lower risk
of developing prostate cancer
that ends up killing them.
And this was true both in white
and black men in this cohort.
We took into account, again, the
number of factors are associated
with risk of developing
prostate cancer,
as well as use of aspirin.
And you might ask, "Well,
what about aspirin use?
It's still associated
with a reduced risk
among statin drug users."
As I've just told you, the
statin drugs are protective.
So, indeed, in fact, even among
those who didn't take a statin,
there's still an aspirin effect.
Now, interestingly enough,
NSAIDs that are not aspirin,
so other non-steroidal
anti-inflammatories
such as ibuprofen,
were not associated
with risk of fatal disease.
Okay? And then among men
who have prostate cancer,
if they took aspirin, they
also had a lower risk of dying
of their prostate cancer.
So we think these are
exciting findings.
Aspirin is not indicated
for cancer prevention
except in one situation.
And that's actually
colorectal cancer
in middle-aged individuals
who have a slightly
higher cardiovascular
or higher cardiovascular risk
for whom aspirin has
already indicated.
And the reason why aspirin use
at this time is not indicated
for cancer in general is because
of the side effects of aspirin.
So GI bleeds, for
example, and also stroke.
Okay? So now on to
periodontal disease.
So why study periodontal
disease?
Well, it's clearly an
inflammatory disease.
There's an immune
component to it.
And so we wanted to know,
this is a collaboration
with a colleague up at
Tufts, she's an expert
in periodontal disease
and cancer,
as well as with dentists.
So this was a new
collaboration for me.
So I'm used to collaborating
with basic scientists
and urologists and
oncologists, and now we've moved
to collaborating with dentists.
And so we were fortunate,
because one of the cohorts
that we work in, they conducted
a dental examination on all
of their participants at one
of their visits, visit four.
So most cohort studies
do not have dental exams
as an integral component
of the work.
So we were super excited
to be able to collaborate
with the dentists who
had performed this work.
And so what did we find?
We found that individuals
who had periodontal disease,
especially severe periodontal
disease, and edentulism,
meaning not having any
teeth, which is often caused
by severe periodontal disease,
had a higher risk of cancer,
very modest, but there
was a dose-response.
And then, in particular,
there were clear patterns
for colorectal cancer
and lung cancer.
This was taking into account
the number of factors related
to periodontal disease
and to cancer,
including colorectal
and lung cancers.
So we were excited about
these findings until you stop
and think, "What is a major risk
factor for periodontal disease?"
It's smoking.
Smoking is also a major
risk factor for cancer.
So what we did is we didn't
just adjust for smoking,
we looked in the never-smokers,
not the non-smokers,
but the never-smokers.
And, sure enough, the patterns
were still there, not as strong,
right, not as clean, but the
patterns were still there.
So we were very excited
about these findings.
And at the end, I'll
tell you a little bit
about what our next steps are.
And so the last story
I want to tell you
about is developing a biomarker
for prostate cancer prognosis.
So prostate cancer is
a very common cancer.
It's the number one
cancer in U.S. men.
It's the number two cause
of cancer death in U.S. men.
At this time, we have few
tools to help us distinguish
which men have disease that's
so aggressive that it needs
to be treated, and which men can
have either a less-aggressive
treatment plan, or
just be watched.
Okay? So, typically, what's
done is on biopsy the patient,
along with his providers,
will determine whether
or not the morphology
of the tissue is
such that the man is
likely to have a higher risk
of progression or not.
And it's a value judgment
for that man whether he
wants to undergo treatment.
Now, if it's a super aggressive
disease, it's metastasized,
that's a different issue.
But if it's early, so
it's working confined,
and the disease doesn't
look particularly aggressive
under the microscope,
there's complexities.
The man has to decide with
his provider what to do
about treatment or
non-treatment.
It would be much
better if we had a tool
that could complement,
it could help men
with their decision-making,
and help providers be able
to give the best option for
management of that patient.
And so years ago
we had a thought.
And this came out of a
discovery in my colleagues' lab,
Angelo De Marzo and Alan Meeker,
Alan is up here, here's Angelo,
where they identified that
throughout the natural history
of prostate cancer there
was increased shortening
of telomere length.
Okay? So the pre-cancer cells
even have shorter telomeres
than the normal cells.
And so they asked the
question, "Could information
about telomere length," --
and telomeres are the
ends of the chromosomes,
and when they shorten that can
lead to chromosomal instability.
And so they asked the
question, "Could information
about how short the
telomeres are
in individual cancer cells
tell us about prognosis?"
And so we came together
to do a cohort study.
So this is a population
science design using real people
who have cancer who are
participating in a cohort study,
the Health Professionals
Follow-Up Study.
We came together to be
able to make measurements,
and then relate these
measurements to risk
of progression to lethal
disease, to metastasis
and death from prostate cancer.
This took a big collaboration.
So it wasn't just our team.
We collaborated with Harvard,
where the Health Professionals
Follow-Up Study is located.
My colleagues, Alan
Meeker and Angelo De Marzo,
had developed a technique.
This technique allowed us
to look at individual cells,
so not looking across the tissue
as a whole, but to be able
to look at individual cancer
cells, individual cells
that are non-cancer cells.
And when I say individual cells,
I mean not just the
individual cell,
but of specific cell types.
Which then allowed us
to explore in detail
which cells are the ones
that were providing
information about prognosis.
And what we found was it
wasn't telomere length
in the cancer cells
that mattered.
It was the variability in
telomere length from cancer cell
to cancer cell that provided
information about prognosis,
along with how short
the telomeres were
in the stromal cells
adjacent to the tumor cells.
And so the stromal cells
were primarily fibroblasts
and smooth muscle cells.
And so what we were able
to do was evaluate about 30
to 50 cells per type,
using a fish approach.
And so these are
beautiful fluorescent scans.
And you can see the pink
dots are the telomeres
and the normal tissue.
And then you can see
in the tumor the pink
dots are very faint,
in some cases you
don't see them at all.
So that indicates the
telomeres are very short.
So here are the original
findings that we had
that were published
a few years ago.
And so I'm going to
draw your attention
to prostate cancer death.
So, again, these are all men
who have prostate cancer.
And what we found was, compared
to men who had less variability
in telomere length
among their cancer cells
and had longer telomeres
in their stroma,
that's the reference group,
those men who had shorter
telomeres in their stroma
and greater cell excelled
variability in telomere length
in their cancer cells, had the
highest risk of progressing
to prostate cancer death.
And this is after taking
into account the known
prognostic indicators.
Men who had the other two
combinations had intermediate
risks of progression.
We found the same pattern for
lethal prostate cancer, but,
interestingly, not for
biochemical recurrence.
A biochemical recurrence
is when the prostate cells
that have escaped from the
prostate before surgery,
I should say all these
men had a prostatectomy,
those cells that escaped in
some men later they start
to produce PSA, prostate
specific antigen.
And while there may not
be evidence of metastases,
this is an early
indication that it's possible
that this man might
eventually develop metastases.
But in most cases they don't.
And so what we want to
be able to do is figure
out which men are most
likely to actually progress
to metastases and death.
So we've now repeated
this work in a number
of additional studies.
And we've put all
the data together
in a form called
a meta-analysis.
And you can see that the
pattern remains the same
for prostate cancer
deaths and for metastases.
And for recurrence, we
don't see the same pattern.
What's popping out
is information
about the variability
in the cancer cell,
but not the stromal cells.
So we're super excited about all
the studies that I've shown you.
These are great examples of
collaboration across disciplines
to discover cancer
risk, protective
and prognostic factors.
And perhaps the most important
part of what I'm going
to tell you is what the
translational opportunities are,
what are the next steps that
our teams together are taking
to take the results that I just
showed you to the next step,
so that we can actually
get these risk
and protective factors
and prognostic factors
to the population for
prevention, or to patients
to help with better
decision-making.
So with respect to statin
drugs and periodontal disease,
our next steps are additional
basic science research.
So we have currently
funded projects to go back
into the laboratory
with respect to statins.
It's to understand how statin
drugs influence a cell that's
related to what John talked
about, T regulatory cells.
T regulatory cells hold back
that autoimmune response.
So they're immunosuppressive.
And we have evidence
from our colleague,
who's an immunologist, that
statin drugs may, in fact,
reduce the immunosuppression
by those T regulatory cells.
So we're going to test with
him directly that hypothesis.
And then for periodontal
disease, with our colleague,
Dominique Michaud up at
Tufts, we received funding
from the American
Association for Cancer Research
to more directly test
whether periodontal pathogens
and the immune response
are related
to lung cancer in particular.
And then the next one for
translational opportunities,
I didn't show you
research we've done to look
at how common risk factors for
cancer development may relate
to cancer outcomes in
people who have the disease.
And, in particular, we've had
an interest in obesity in men
with prostate cancer, and how
that may relate to
their prognosis.
And so what we've found
over several studies is
that obese men, and
especially men who gain weight
from before their
diagnosis to after,
have a much higher
risk of progression.
And so my colleague
just received funding
to conduct an intervention
study to take men
who have prostate cancer,
who have early recurrence,
that's biochemical
recurrence, and then she's going
to randomize them to a lifestyle
intervention for weight loss
versus standard of care, and see
if that affects their
outcomes with prostate cancer.
So that's developing and
testing strategies to intervene
to reduce the burden of cancer.
Another example is the
telomere biomarkers.
So what are we doing next?
We've developed the biomarker.
We've actually optimized
it for use.
The question is, "Well, what is
the use beyond just being able
to say to a man, 'Here's what
we think your prognosis is.'?"
Does it have any role in helping
for treatment decision-making.
And we actually think
that it does.
We think the biomarker
is telling us something
about disease biology.
So we've just submitted
a grant application
to determine whether the
telomere biomarker will give us
information about which men,
who've started to recur,
the PSA has gone up again,
which men would benefit
from simple salvage
radiation therapy,
and which men would benefit
from additionally having
anti-androgen therapy on top.
And the reason why not all men
are given anti-androgen therapy
in the first place when
they start to recur is
because it does have
side effects.
And so to figure out
which men would benefit
versus which men would
not would be an advance
in the care of those men.
And then the last
one, as I mentioned,
we have optimized the
telomere biomarker.
And we had funding to do that.
So thank you for listening.
Here are the acknowledgments,
the funding
and then our colleagues, an
example of our joint lab meeting
that has our basic
scientists, our urologists
and our population
scientists who come together
to study the problem of cancer,
and in particular
prostate cancer.
Thank you.
[ Applause ]
>> Tomoko Steen:
Thank you so much.
Thank you so much.
So our third speaker is
very close to our patients.
Actually she's a clinician.
She's a [inaudible]
clinical investigator,
Division of Hematology
and Oncology.
And she's also director of the
Translational Cancer Medicine,
and head of the [inaudible]
Therapeutic Section
at Columbia Medical School.
And she was at the
National Cancer Institute.
And she has done significant
discoveries and studies.
And her work is epigenetic
modification agents,
as well as her group
received approval
by the FDA for [inaudible].
That was a medicine originally
developed by Japanese scientists
for the antibiotics purpose,
but it was too potent.
And her group got approval for
[inaudible] T cell lymphoma,
as well as peripheral
T cell lymphoma.
And she has been working now
at Columbia still a combination
of laboratory studies
and clinical studies.
So she has a goal to
translate the ideas
from the laboratory
to clinical trials.
So, Susan, thank you so much.
>> Susan Bates: Thank
you very much.
Thank you.
I really enjoyed
those last two talks.
And I hope we can find
the third [inaudible].
[ Inaudible Speakers ]
So what I've been
doing since I went
to Columbia is actually working
more on pancreatic cancer.
It's a very, very
difficult disease.
And I have learned an
enormous amount about it.
And I wanted to just talk
to you some about that.
That is completely
translational,
trying to identify strategies
to try to bring to patients.
Anyone know anyone who's
ever had pancreatic cancer?
So you've known some people.
So it's not a commonly
diagnosed disease as others,
as you can see here on the
slide, where only 3% of patients
who are diagnosed with it,
of all 1.7 million cancer
diagnoses expected this year.
But, in fact, it accounts
for a larger fraction
of patients who die from cancer.
And it's on target to become
the third leading cause of death
from cancer in general.
So it is very important that we
try to start figuring out how
to solve the problems
of pancreatic cancer.
This is the five-year survival
from -- oh, my goodness.
Sorry. I don't know
how that happened.
Oh, my. This is the
wrong version.
This is completely
the wrong version.
So I'm going to have to give
you a different version.
I'm sorry.
[inaudible] to do that.
I guess we can keep talking.
This is totally the
wrong version.
I apologize.
So I had my husband
give me some edits,
and all he ever edits is font.
The font, that's
all he ever edits.
So the problem with
pancreatic cancer --
I'm going to get
my computer open
and I'll talk at the same time.
[ Inaudible Speaker ]
So the point about
pancreatic cancer is
that it's a big problem
because of the local disease.
Yeah, you can [inaudible].
It has the local disease,
it has distant disease,
and it is drug resistant.
And then we have
problems with --
and we have made progress
in precision medicine
and immunotherapy, but
we have not made the kind
of progress that
we need to make.
And that's what we'll
be talking about.
So the local disease,
probably the pancreas,
is it's nestled right
up under the --
right up under the liver --
It's going to be the
last [inaudible].
Right up under the liver, where
the bile drains from the liver,
part of the digestive process,
into the small intestine.
And the pancreas sits
here, right nestled
in behind the stomach.
And then when you
get a cancer there,
it's actually sometimes
diagnosed very early,
unlike other cancers
in the body.
It can be diagnosed when
it's one or two centimeters,
because it is in such
a vital location.
But that doesn't seem to make a
big difference in what happens,
because the recurrence
rates are very, very high.
The recurrence rates --
[ Inaudible Speakers ]
Recurrence rates are very high.
And the reason they are high
is that it is a distant disease
from the very beginning.
So while people think, "Oh,
this is a two-centimeter
pancreatic cancer,
I should be able to get that out
and cure the patient," in fact,
what happens is that the tumor
cells have already escaped
into lymph nodes, this is
a drawing of a lymph node,
escaped into the bloodstream
and traveled to the liver,
and set up what we call
micrometastatic disease
in the liver and in the lung.
And, in fact, 75% of patients
are not candidates for surgery,
because it's already invaded
into those local structures,
because it's right next
to everything that matters
in your digestion, and
also because it very soon,
very rapidly travels
into the bloodstream.
So 75% don't get surgery.
And I tell this to
patients all the time,
"You're in the lucky
25% of those
who do get to go to surgery."
And then I try to gently tell
them, "But there's a 75% chance
that you're going to die
of this disease anyway."
So that makes that 8%
5-year survival a reality.
It really is a death sentence.
This is a very difficult
disease.
So it's drug sensitive, but
we do have drugs for it,
like we do with other cancers.
Which for many years, when I was
in medical school,
there were no drugs.
No one thought that
pancreatic cancer would respond
to anything.
But now we have found,
eventually,
that there are a couple
of treatment regimens.
And these are a bunch
of different patients,
where we have response of the
tumor, it shrinks in size,
and then it grows back.
Response, grows back, response,
grows back, response,
grows back.
So you can see that the majority
of the time it grows back
by about -- it really
starts turning
around by 100 to 200 days.
So that means three
to six months.
So by the time I'm
kind of relaxing
and I think I've got this
patient on autopilot,
they're getting their
chemotherapy,
the scan comes back and tells
me I've got disease progression.
And I have to start all over.
And that is the life of the
patient with pancreatic cancer.
Once you start down that road,
it's a never-ceasing source
of the cancer's going to respond
to treatment, but it's going
to come back, until eventually
we run out of treatment.
So there it took
actually research.
The concept of how
difficult it is
to do clinical research
sometimes amazes me.
And I've been doing it
for all these years.
But I sat down once and I added
up all the patients enrolled
in the clinical trials
that it took to find
that one drug combination
called for Folfirinox was better
than Gemcitabine, and
a two-drug combination,
Paclitaxel with Gemcitabine, is
better than Gemcitabine alone.
So these are our two
leading drug combinations.
So better than a single agent.
It took, basically, 40 clinical
trials and 14,000 patients
to get to the point of
proving that, because over
and over again we tried and we
failed, we tried and we failed.
And we, finally, got
two regimens to try
to treat these patients with.
[ Inaudible Speakers ]
My computer's so full.
And this is just the benefit
that we got out of these two,
that in terms of survival.
That's how we measure
overall survival
and how we measure a
benefit in pancreatic cancer.
We don't have to measure how
good does this drug work,
how to shrink the tumor.
We just have to measure did it
make you live longer or not.
And that's a devastating
comment in itself.
The FDA has spent
enormous effort trying
to accept other endpoints for
other diseases, tumor shrinkage,
a disappearance of
tumor, various things.
And pancreatic cancer
is one thing.
It doesn't make you live longer.
And so these are the
two chemotherapies.
And this is for people
who couldn't go to surgery
where the disease was
spread outside the pancreas.
So in those patients, it made
you definitely increase survival
by four months, live from,
basically, seven to 11 months.
And this is one of the reasons,
it's not the only reason,
but you heard about lymphocytes
and lymphocytes being
in cancer cells.
So this is one example
of a pancreatic cancer
where there are plenty of
lymphocytes or immune cells,
those T cells, and up
here is the cancer.
But what you can see is
that there's a lot
of fibrous material.
It's actually called
hyaluronic acid.
Dermatologists use it to
make your cheeks puffier
when you see people that
have been to dermatologists.
And it actually prevents
those --
we think prevents
those lymphocytes
and from getting
into the tumor cells.
So the question is, "Can we do
better with precision medicine?"
And that's where -- okay --
[ Inaudible Speakers ]
Well, we'll see.
[ Inaudible Speaker ]
I'll just talk when I
-- I have such lovely,
better slides than this.
It might be that I
sent you two versions.
I probably send you the
correct one the first time.
So I don't know if you have
that on your flash drive.
[ Inaudible Speakers ]
Yeah, yeah.
Did you save both versions
I sent you this morning?
[ Inaudible Speaker ]
Because maybe I sent
you -- it was very --
[ Inaudible Speaker ]
They were identical?
Okay. Anyway, so what
we're going to be talking
about now is precision medicine,
and how that relates
to pancreatic cancer.
So what we've done
in oncology is,
as a result of the Cancer
Moonshot, as a result of a lot
of fabulous progress that
you've heard about already,
we've learned to figure
out specific changes
in patients' cancers that lead
to help drive that cancer,
and that we can identify
a drug that will target
that cancer, and have succeeded.
So that's called
targeted therapy.
That's how we've
come to call it.
Precision medicine and
targeted therapy are,
basically, the same thing.
And a lot of, for example,
the American Cancer Society
in trying to explain
what is targeted therapy,
they say these drugs target
certain parts of cancer cells
that make them different
from other cells,
or they may target other cells
that help cancer cells grow.
But it's a specific target,
as opposed to our traditional
chemotherapy, which --
[ Inaudible Speakers ]
So that's different from
traditional chemotherapy,
which binds DNA, binds
tubulin, binds something
in the cancer cell,
and the cancer cell has
to be more vulnerable
to being killed.
This is something that
makes the cancer a cancer.
And that's the reason why
we call it targeted therapy.
So it is clearly a validated
treatment in some tumors.
This is just an example
that I got from a website
where they're showing if we take
a number of patients who have,
for example, lung cancer,
we know that some are going
to have what we call an
EGF receptor mutation,
some are going to have what
we call an ALK mutation,
different changes in cancers
that lead them to be different,
so they're alterations that
lead them to be susceptible
to different treatments.
So the key here, though, is that
this person has to be identified
as having had the EGF receptor
mutation, and this person has
to be identified as
having an ALK mutation.
So we have clear examples
where it's become a real
cancer medicine by doing that.
We know that in chronic
myelogenous leukemia we can
treat patients with Imatinib
that inhibits this protein.
And patients now are not
even dying from the disease.
It's turned it completely
into a chronic disease.
We know that in breast cancer
patients with HER2-positive,
that's a mutation or an
amplification of HER2,
they have very good, very
long treatment responses
with an antibody against that.
Erlotinib and Gefitinib.
And I'm going to show
you more about that.
And then a melanoma
mutation against BRAF
that I'm sure you've
seen in the news.
So here's the mutation.
EGF receptor signals
cancer cell proliferation,
cancer cell survival.
It makes the cancer grow.
It's a ghost signal for
the cancer as a whole.
And that EGF receptor
mutation is the one
that we can specifically target
with EGF receptor inhibitors,
Erlotinib, Gefitinib, drugs
that are FDA-approved.
These make people live longer.
It converts their disease,
at least for a time,
into a responsive disease.
And then other cancer drivers
have been eventually recognized.
Targeted therapy for all of
these has been developed --
for most of these
has been developed.
Not for all of them.
But they are effective.
They're not curative.
But it has been a
watershed for lung cancer.
It completely changed it from
the kind of disease we talked
about earlier where no benefit
to a disease where we have drugs
that target it that
hold the disease at bay.
So if we don't get to the
end of it, we'll be okay.
You think you've got it loaded?
Okay. [inaudible], but
let's wait and see.
Maybe I somehow just got
the whole thing tangled up.
So what people have done
then, and now this is
where personalized
medicine, basically,
went out into the community,
before we were completely ready
for it to be there, but it went
because every patient wanted
to know what was in
their cancer genome,
what caused my cancer,
what is my cancer.
So many different institutions
have developed their own 500
cancer gene panel.
There's agreement that about
400 genes are cancer genes.
And the people took it on their
own to develop their own panel
for whole genome sequencing.
Columbia has its own.
Memorial Sloan Kettering
has its own.
University of California
San Francisco has its own.
FoundationOne is the
most widely used.
And so these actually cost
an enormous amount of money.
And patients want to
know, and they hope
that that will give
them information
that will lead them
to a treatment.
Now, what comes back on
these cancer panels --
[ Inaudible Speakers ]
Okay. So can we switch to the --
can we switch over to the other
[inaudible] that she saved?
I'm sorry.
I know this is taking
[inaudible].
[ Inaudible Speakers ]
I'm sorry.
And that's the last time I let
my husband work on my talk.
[inaudible] a big [inaudible]
like that [inaudible].
He's also a physician.
So what those 500 gene
panels do is they are looking
for all different
kinds of mutations.
They're looking for
many more things
than just individual mutations.
But the thing that we look
the most for is where,
at the DNA level, you have
one base change that leads
to a change, potentially.
It can be [inaudible]
in the RNA,
and leads to a change
in the amino acid.
Those are called missense.
It doesn't, we think, really
hurt if it changes a base
that doesn't change
the amino acid.
Sometimes it causes
a change that leads
to the protein not
being synthesized,
and the loss of a protein.
So these things can all
be related to cancer.
And that's what we get back
from our 500 gene panel.
So this is a patient of
mine with pancreatic cancer
who we ran the Columbia
panel on.
This is the kind of
result we get back.
Four hundred and
sixty-seven cancer genes.
We have mutations in KRAS,
TP53, SMARCA4, CDKN2A.
So a whole bunch of genes.
Some I don't even
know what they are.
I don't know what
all these genes are.
And that's what your
doctor is getting back
when you sent your
thing to FoundationOne,
he's getting back a report
just like this with all kinds
of genes that you don't
actually know what it has.
And so you get the report back,
and they classify these
variants, and they say, "Well,
some are unknown mutation,"
like the EGFR mutation
that I showed you.
And there's an FDA-approved
drug for it.
And if you have lung cancer,
it's an FDA-approved indication.
So in that situation,
bingo, you're settled.
But many of them are
it's an EGFR mutation.
There's an FDA-approved drug,
but it's a different tumor type.
Is that the same thing?
We actually don't know.
And sometimes it comes
back a known mutation,
but there's no FDA-approved
drug.
And sometimes, as with many
of these, I have no idea what
that gene is, or what the
mutation is doing there.
So the problem with that
is that it's a $5,000 test.
And we're, basically, running
$5,000 worth of experiments
on lots of patients without
actually knowing the outcome.
So the precision
medicine strategy is
to take a newly diagnosed
cancer, and find out which
of these categories
it really fits in.
Is it a known mutation
in a known tumor type
with an approved drug?
Great. Or is it a known mutation
in a different tumor type,
in which case the doctor has
to work hard to get the drug
and off-label use,
but you can do that.
I've done that.
And I actually did
it for that patient.
And I picked this one because
there's a breast cancer drug
called palbociclib.
Now, I could have picked this
one, but there's a drug that's
in clinical trials that
might work against that.
That would be a lot
harder for me to get
that than an FDA-approved drug.
But you see I have no
data for either choice.
And then there can be a
completely unknown mutation.
So I've already alluded
to some of the problems
with where we are with
precision medicine.
It sounds great.
We all want it.
We all absolutely want it.
Every day when I see patients,
I want to order the
tests for the patients.
But the truth is
knowing the mutation,
it may have a different role
in the tumor I'm looking at.
Many mutations can be
found, not just one.
We don't have drugs
for most mutations.
And when we direct a patient
toward a targeted mutation,
we direct that patient away
from the proven therapy.
It's new. It's expensive.
And patients and insurers
pay precious dollars
for what's effectively
an experiment.
Now here's where I'm going to
show you how it's an experiment.
So BRAF in metastatic
melanoma, a fabulous discovery,
that most melanomas have BRAF.
It's driving the cancer to grow.
And when we treat with a
drug called vemurafenib,
or BRAF inhibitor, it
turns off the signaling.
It went from bright
on this glucose scan,
all these are spots that
patient had all over his body,
and now they resolved.
It doesn't work forever,
but it works.
And this is the whole patient.
This is the way we
show patient responses,
called a waterfall plot, where
it's the percent shrinkage.
So patients didn't have
100% shrinkage, typically.
Some did. But many had a
fraction of that percentage.
I mean, this is a
fabulous waterfall plot.
And it made people live longer.
Those who got the drug lived
longer than those who didn't.
So then they said,
"Well, this mutation shows
up in lots of other cancers.
We're going to practice
precision medicine
on those other non-melanoma
cancers."
So the biggest group that
also has this BRAF has
colorectal cancer.
And, in fact, there were six
patients that had shrinkage.
Nothing like you saw in
the waterfall plot before.
This looks totally different.
And, in fact, they all returned
to baseline by one month.
It wasn't by 11 or 12 months.
So this did not succeed at all.
This was a total failure.
And, in fact, a number of
people said they took a broader
approach and they said, "I'm
going to do the FoundationOne
in a variety of patients,
and then give them all
the best drug I can think
of with the FoundationOne
precision medicine strategy.
And I'm going to see
if they live longer."
And so they collected
all those patients.
And, really, there's very little
difference between those curves.
It has a ratio of
.88 is, basically,
saying almost no difference.
So precision medicine,
we have to think about --
we cannot think of that right
now as the answer to everything.
What we have to do is keep
looking for actual targets
in tumors that are
drivers in most tumors.
So this is pancreatic cancer.
And this is a sequencing
of about 400 patients.
And these are a variety of genes
that were found to be in one
or two percent of
those patients.
But there is a gene called KRAS.
Very similar to that
EGF receptor.
It drives growth, drives
size, drives metabolism.
It's found in pancreatic
cancer almost always
at the very beginning.
It's the first gene
that changes.
So it is a key gene.
And the NCI actually has set
up something called the
RAS Initiative to try
to find a drug for this.
But we don't yet have one.
Now, RAS signals
a lot of things.
It signals through ERK,
which is in that BRAF.
But it signals down to
a protein called MYC.
MYC is highly expressed
in pancreatic cancer.
And when it is expressed
at very high levels,
you actually have a lot
more patients dying.
This is a survival curve.
This is more survival,
this is less survival.
So patients with pancreatic
cancer have less survival
when you have active
signaling through MYC.
So one of the things my
laboratory now is working
on is a compound that will turn
off MYC in pancreatic cancer.
And you can see here,
this is a western blot
of protein expression.
You can see very
high MYC expression,
and then you see
how it's turned off.
Very high and how
it's turned off.
It also kills those cells,
at least some of them.
Some are not very sensitive.
This is a killing curve
of pancreatic cancer
cells in the laboratory.
And we start out at 100%.
And at least two
of the cell lines
that we study are very simple.
But we're stuck in this research
because we need $50,000
to make this drug.
And we don't have it.
And we keep putting in
grants over and over again.
And we still aren't
getting a grant back
to finish this research.
So if any of you
have any influence
over directing dollars toward
pancreatic cancer research,
think about that.
So my patients always come
back and they say, "Okay,
what about immunotherapy?
I want a treatment.
I want immunotherapy."
And you saw this a
little bit earlier.
The way I think about this --
see here's the big tumor cell,
the little bitty T
cells, which is amazing.
All these drawings,
the T cell is no match
for the cancer cell
in terms of size.
There's this handshake.
I call it a handshake
that is, basically,
this tumor telling this
T cell not to be active.
You saw the inflammation
that we talked about earlier
that you need to have.
Well, when we add those new
drugs that are FDA-approved,
you block that handshake, and
then you get T cell activation.
And the tumor dies.
So the T cell feeds things
into this tumor cell
that make it die.
And so we want to block the
handshake that turns off
so that the T cells can
attack the tumor cell.
Well, this is what -- I
got this off of Google
and then I couldn't refine it,
but someone had drawn it showing
that immunotherapy -- it's
a great time in oncology
because of immunotherapy.
You can see that they've drawn
this 100% survival curve,
dropping [inaudible].
So 80% of patients are living
because of immunotherapy.
Whereas without it,
patients die.
Whereas this is so much better
than traditional
cancer treatment.
Right? How many believe this?
I've got some land in
the swamp to sell you.
So, okay, there are patients
who've done amazingly well
with immunotherapy.
But it is not 80% of patients.
The reality is far closer
to this than it is to this.
So that's one problem we, who've
developed small molecules have,
"Well, your grant doesn't
even have immunotherapy in it.
You just want to develop
a small molecule."
So the reality is that
immunotherapy is not helping.
Only in melanoma is it able
to even approach the
majority of patients.
Every other disease, it is
much closer to this reality.
But I'm not trying
to be negative.
There are lots of
other handshakes
that need to be studied.
And all the things that
you talked about --
Dr. Tsang talked about in terms
of why people respond,
why they don't.
But too much in -- to my mind,
there's too much energy
currently invested
in immunotherapy, and not
enough back in small molecules,
back making the precision
medicine dream a reality.
There are still other oncogenic
drivers that need drugs.
And that's the work I
think is so important.
So we have 361 clinical
trials, including ten that are
in exactly the same category
of the exact same handshake
that we already have very
good drugs FDA-approved for.
So we need new immunotherapy,
different immunotherapy.
And we need more small
molecules to be developed.
So just to sum up,
pancreatic cancer's on track
to become the third leading
cause of death from cancer.
Surgery's not enough.
Responsiveness to
chemotherapy, yes, it's there,
but it rapidly develops
resistance.
Precision medicine
and immunotherapy are
works in progress.
And research funding is critical
to make progress
in this disease.
So to sum up, I have a lot
of people that have helped me
with all the work that we do.
A lot of people at Columbia.
Just been blessed with many,
many collaborators
over the years.
Thank you.
[ Applause ]
I'm sorry for the confusion.
I don't know those two
slides got in there.
I'm completely baffled.
All right.
And that slowed us down, too.
I apologize for that.
[ Inaudible Speakers ]
>> Juanita Lyle: Good afternoon.
Welcome back to our third
Cancer Moonshot Program.
It gives me great pleasure to
be here in the midst of progress
that I had hoped to
see and continue.
I have surpassed the
time of being a recipient
of such a wonderful
good news time
with the Cancer Moonshot
Initiative.
I came from times
that things were still
in the research process
and sheer experimentation.
Now everything to be here --
to be now progress with
this Cancer Moonshot.
Now it's today it's more about
the treatment of the patient
than the treatment of the
patient with the disease.
So I welcome aboard today
John Bauer, [inaudible] club
of the big little c. I told John
that the reason why I
called it the big c is
because it becomes the little
c as we go through the process
of beating the disease itself.
Meaning sometimes it
looks too big to defeat,
but when you do it, it
becomes something little
to kick to the curb.
John Bauer has walked
the journey
of the c. He started working
in the Library in 2010.
He started his journey in 2014
with thyroid, head
and neck cancer.
Fortunately, they were
treatable and curable.
He, like I, did all the right
things with food and fitness.
He is a father and husband
with three young children.
I, of course, was a
mother and wife in 1976
with a six-year-old daughter
and an eight-year-old son.
But I look at John today, and
John is [inaudible], John,
welcome to thriving
in survivorship.
So John it's you're
moment to share now.
[ Applause ]
[ Inaudible Speakers ]
>> John Bauer: So I can't
offer any cures for cancer.
But there's no -- I know
nothing about telomeres
or [inaudible] or any of that.
But I do offer a
perspective from a patient.
And, hopefully, offer a better
engagement on physicians' part
and researchers'
part with patients.
And also to offer patients
a better ability to cope
with the situation at hand,
which can be devastating,
of course.
So I just borrowed the
title page here from --
[ Inaudible Speakers ]
Got it. Thank you.
Okay. I'm an IT guy.
I don't do too many
presentations.
So, anyway, that slide's
just to start it up.
I didn't know --
the guidance was
to convey my own
personal experience,
but also to emphasize
the engagements
with medical personnel
along the way.
So I thought how do I do this in
an engaging and thoughtful way?
Cancer is kind of
in the same category
as 9/11 or the Holocaust.
And it's just, you
don't joke about it.
It's just too dreadful
and it's pernicious.
And as affected as
people are by it,
it certainly doesn't lend
itself to standup comedy.
But, nevertheless, I did try
to put together something
that was entertaining
and thoughtful.
So here we go.
Here's my dad and I
in the early '60s.
And then my dad was swept up
in 1969 in the Vietnam War,
and he was exposed
to Agent Orange.
Myself, I was doing
okay until 1985.
When Chernobyl hit,
I was studying German
in a small German village.
And Chernobyl happened.
I knew it happened.
I didn't know exactly
how serious it was.
Nobody really did at the time.
They just picked up some sensors
in [inaudible] had picked it up.
And the cloud was rolling
across Eastern Europe.
And it was really unsure
how serious it was.
The German politicians were
assuring everybody [foreign
language], don't
worry about anything.
Everybody stay put.
How are you going to evacuate
millions of people anyway?
So I thought, "Okay, I'm
going to sit this one out."
But then I saw my classmates
coming back up from Switzerland
from hitchhiking,
[foreign language],
which is okay to
do in Switzerland.
And half their face
was completely burned,
just burned to a crisp.
And the other half was
completely unaffected.
So I knew something -- that
was the side that was pointing
where the cloud was rolling in.
So I thought, "Okay, it's
time say auf wiedersehen
and jump on the plane."
So my Iceland air flight, my
chief Iceland air flight I had,
I wasn't due to return
until months later
after the study concluded.
I found myself up in Iceland.
I thought, "Oh, great.
Up in Iceland, I'm home free."
The cloud's not going to
make it up here, certainly.
But then when I discovered later
that Iceland took a
really big hit, of course,
I was outdoors admiring
waterfalls
and doing all the
Icelandic things.
So if I had to take
a guess of what --
have the thyroid
cancer [inaudible].
I tried to get iodine.
Of course, nobody spoke English,
and there wasn't
any iodine on hand.
What they had went
to Icelanders.
I couldn't get iodine.
Okay. So in any event -- because
I know iodine, of course,
soaks up the radiation,
it flushes it
out without it affecting.
Okay. Fast forward to 2004.
My dad, by the way, his cancer
started in the early '90s.
And his second wife
was a Thai doctorate
who had professional
commitments back home.
So he moved with
her back to Bangkok.
And I get this call, it was
actually May 2004, late May.
My twins were born by
in vitro fertilization.
That's a different story.
August 2004 I get
the dreaded call
that every son or
daughter dreads.
I'm in the shower
and getting ready
for work on a Monday morning.
And my wife comes running
in, "John, come quick.
Your dad's in trouble,"
et cetera.
So I hop on the next
plane to Bangkok.
I was by myself at the
Faculty of Medicine
at Ramathibodi Hospital, where
my dad had formed friendships
with the research staff there.
And he would grade
their papers --
he would edit their
research papers in return
for them keeping him alive.
And it was a good
exchange, a good arrangement.
They keep him on
the latest drug,
and until that drug
stopped working.
Then another one
would come along.
And they managed to prolong
his life for ten years
because they caught -- back
in America they caught
his condition late,
so it had progressed.
And here they are
here, the physicians.
They used Mr. Robert.
They addressed you
by your first name.
This is the ICU chart.
He was in ICU when I arrived.
This was taken later
so I'm smiling.
And, of course, everybody
in Thailand smiles.
So she's the ICU nurse, the
hardest job in the entire world.
And I went back to
thank her afterwards.
So this is a bit
of a staged photo.
This didn't happen as I arrived.
It wasn't [inaudible] arrival.
The IXU chief at one
point, as my dad had a tube
down his throat, and he
had a needle in his neck
because they would have
to transfer [inaudible]
every couple of days.
And they were just, basically,
artificially keeping him alive.
And the ICU chief -- this
went on for several days.
And his heart was strong.
And I, you know, "What do I do?
I never -- in a new
situation -- you had to know."
The ICU chief pulls me aside,
and he laid down the law
with his, read me the riot act.
And he said, "There
comes a point
at which we're no
longer extending life,
that were prolonging death."
And I said, "Right."
So I took a walk around
Bangkok with his doctors.
And I said, "What do I do?"
And they said, "Well,
do what we all do,
and just make the
hard decision."
And I said, "Okay, when
would you like to do this?"
She said, "Whenever you like."
And I said, "Well,
how about tonight?"
"Yeah, okay, great."
So they put out the word.
All his friends, every friend he
had in the world at that point,
gathered in the ICU room.
And a fellow came
in with a syringe,
and I held his hand
as he passed.
And I had a certain amount
of engagement with him
when his eyes were still open.
And I was able to communicate
everything I needed to say.
But it was certainly a one-sided
conversation with a tube
down his throat, there was no
argument or anything involved.
But, anyway, so here's
the temple.
I'm going to blast through
these quite quickly just to kind
of show you what it involved.
And on this thought
everybody says, "Well,
we're praying for you."
Regardless of religious belief,
it's more of a coping mechanism
on their part, really,
because what can people say?
I mean, this person has
cancer, for heaven's sake.
You don't want to say, "You're
going to be fine," or, "Well,
you shouldn't have
this to drink.
You shouldn't of
drank Gatorade."
I don't know.
But, really, the discomfort
was in everybody being required
to confront their own mortality.
And I think it's
really more for them.
I said, "Oh, thank
you, thank you.
I'm not a religious person.
[inaudible] a spiritual person.
Thank you, thank you."
But just to hedge my bet I
did have prayer groups going
in all major world religions
pulling for me there.
And, ultimately, it worked.
So, again, here's
back in my day.
This is [inaudible] momento
where we flashed back
and flashed forward [inaudible].
You never really
know where you are
in the presentation at the time.
But I managed to get the
point across at the end.
So here's a [inaudible].
I had it [inaudible],
sorry, picture of him.
I think it was midsummer
heat, Bangkok, Thailand.
Full uniform, he's got
a cigarette hanging
out of his mouth.
He's doing his work.
Look, I don't get it.
His job is to cremate.
So they arrange the
bones in a certain order,
sprinkle some nice roses
and pebbles on them.
And then they box it up.
And it wasn't all bad.
This was back when I ate meat.
This is a fish.
Well, it was a fish.
And it was just delicious.
Anyway, fast forward to
2014, and I'm diagnosed.
And I said [inaudible]
first commenter was, "John,
we're just in a state
of disbelief
with your list of
health hang ups.
You're the last person that
this should happen to."
I agree, because since college
days ended, since I met my wife
and got serious about life,
I tend to follow a fairly
healthy diet regime.
I certainly never smoked.
Drinking was a thing
of the past, et cetera.
So, anyway, I find
myself several surgeries,
27 lymph nodes, 36
radiation treatments
and various chemotherapy
appointments later,
I find myself in this
treatment program here.
So here are the kids.
And it was another everybody
says is, "Oh, you're so brave."
And I'm thinking, "Right.
[inaudible] my choices
are exactly?"
So kind of as a patient, you're
kind of along for the ride.
And I was really actually
measuring up the pine box,
because I personally
didn't expect to survive.
I was, like, they say
prepare for the worst
and hope for the best.
So there I was.
And it's a bit like they did
[inaudible] in the foxhole,
the battlefield, when
they hear the charge,
and you can't see
in the foxhole.
You've got to advance.
So this is a [inaudible].
So they locked and bolted me
in in one these [inaudible] my
little custom-made headset here
where they bolted you in.
And, of course, just
what I needed
after Chernobyl was
more radiation.
But, anyway, [inaudible].
And these are the
fellows that helped.
There I am after it.
You see the sunken eyes
and just thin as a bone.
I mean, just absolutely
-- just absolutely --
and the kids they [inaudible]
the best they could.
[inaudible] the Legos.
It was actually [inaudible]
where they took me away
and where they put out
the call for prayers,
because John may not make it.
There was blood on the wall
where I'd walked into it,
and I just had no memory of it.
And I just -- it
was [inaudible].
I just want to [inaudible] say
cancer affects not just the
individual, but instead
the whole family.
And it's the cancer patients
that have a support
structure in place.
But the caregivers don't.
So it really affects the family,
really most of the family.
The patient, himself or
herself, is really just kind
of along for the ride.
And maybe I'll survive
this and maybe I won't.
But let's give it my best shot.
You see, here's my youngest son.
He's about 11, ten
or 11 at the time.
And he's giving me the
feeding tube there.
And here's my little guy.
Evidently any fertility
issues were overcome in 2010,
the same week I joined
the Library,
coincidentally, it
was a good week.
When he was born on
my 48th birthday.
So, anyway, the kids
would take [inaudible].
They wouldn't do this now,
because the twins
are 14 [inaudible].
But back in the day they would
keep me warm and whatnot,
because I was suffering
temperature issues.
This [inaudible] certificate.
I barely squeaked
through college,
freshman-level chemistry.
So I'm the least qualified
person to grace the stage today.
But, obviously, my
talents lie in other areas.
But of all these certificates
and awards and diplomas
and whatnot that are
on my wall of shame,
this is probably my
hardest earned, was this.
And it talks about a
hero at the bottom.
It says here [inaudible]
it says, "Here was a person
that takes personal risks
through their own
life to save others."
And that never really occurred.
I was just kind of in
it for what I could get
out of it, basically, surviving.
Here's a little guy
ringing the gong
in the radiation
oncology waiting room
at the end of treatment.
Okay. Now, 2015, this is
another very important point.
Recovery is way harder
than treatment.
Again, in treatment you're
just along for the ride.
You do what you're told.
And you take what's given you.
But recovery, you're,
basically, on your own.
That's when you have -- you're
suffering this chemo brain,
and you're sitting
in meetings at work,
and you just can't string
two thoughts together.
And it's like you can't
formulate sentences.
And it's just life
is very difficult.
And you're still
smelling burning flesh
from the radiation.
And it's just getting these
chemicals out of the body,
because I really, like I
say, [inaudible] vegetarian,
you're drinking filtered water
and never drinking
bottled water.
There's some hang
ups a mile long.
But the point is that I tried to
run a clean ship, and suddenly,
as the chemotherapist told
me, he said, "You've been,
basically, poisoned with
the nastiest stuff known
to man to get rid of this."
This was all for a good cause.
Here's the [inaudible].
This is, again, a staged
shot after the fact.
And the radiation oncologist
said something to me
at one point in the treatment,
"You have to prepare yourself
for a life after cancer."
I just thought that's
a radical thought.
I'm prepared to die
here, and you're talking
about life after cancer.
I can't see beyond
the next appointment.
So that was just
a radical thought.
And I took it upon myself to
really make those extra 100 days
or 200 days or whatever,
providing you don't have a tube
down the throat, providing
they're mobile and [inaudible]
and whatnot, it's worth
it, so they can wring
that extra little
bit out of life.
I don't mean to go all
Joseph Campbell on you,
the hero's journey sort
of thing, but, really,
that's what it amounts to.
So, basically, I sprinkled this.
I thought, "What do I
do to keep [inaudible].
Photographs, sprinkle
it with metaphors,
various quotes and whatnot.
Get my point across and
it will all come together.
Great." So here we
are, me and the twins.
The little guy he said he
had to stay home with Mama
because I knew from
visiting [inaudible] before
that he would not be able
to navigate squat toilets.
Here's the daughter
busting a move here,
she's a little yoga [inaudible].
There she is at the Taj Mahal.
Little fellow.
Okay. These guys, [inaudible].
Basically, they don't have
any family or any job,
and they just, basically, embark
on this internal quest in life.
And they don't have
any sort of home.
They're accounted for
as homeless people.
But they dress up in really
bright colors, a lot of makeup,
and they they smoke
a lot of dope.
I mean, a lot of dope.
And they're constantly stoned.
It's like Elon Musk says,
"That's why they
call it a stone,
because you sit there
like a stone."
Okay. So, anyway, the
oncologist's initial consult --
okay, now, they've already
exhausted conversationally the
introduction and the how do
you do's and the qualification.
Okay. Then the possibility
of genetic treatment
has been set aside,
because that's not going to
work [inaudible] conventional
[inaudible] getting it.
He shows me a laminated flow
chart showing cancer type
and stage, easily
accepted surgery, radiology
and chemotherapy protocol.
So I thought, "Okay, right,
we're going to do
this the old way.
We're going to cut it out.
We're going to burn it out.
And we're going to poison it.
Right?" And I'm thinking,
"Okay."
So he shows me on this chart,
and it was very comforting
actually, you are here.
You can expect trouble
swallowing
and talking here
elsewhere on the chart.
Since we can't operate
during treatment,
you'll need a feeding
tube starting here.
And I thought, "Oh, my God,
you're not going to be able
to swallow your food."
So okay, great.
I said, "I see."
And I just -- I don't know, it
seems like it's all in the news,
this medical marijuana,
miracle [inaudible].
I live in Virginia.
It's going to be last
state in the union
that [inaudible] marijuana.
But I said, "What about
medical marijuana?"
And he says, "Look, I
don't want to be known
as the doctor who
prescribes pot."
So it's all about reputation.
And I get it.
"And the last thing I need
is a paranoid patient calling
the office."
And I tried to make
the case here.
I argued, "Look, I'm
already losing weight.
I understand Drabinol,
I've done all my research,
which every doctor
hates probably.
It stimulates the appetite.
Because already my
pants were falling off.
So I had to drill
extra holes in my belt.
My co-workers said,
"Hmm, you might want
to get that checked out."
Anyway, he said, "Rest assured,
you'll get whatever you need
to get you through this."
So I found that very comforting.
So here we are, morning
sunrise on the Ganges, goats,
interacting with the
folks from [inaudible].
This was done on a budget,
I want to emphasize,
a backpacker's budget.
We only flew to where
there weren't roads,
or where there were bandits,
or 1,000-drop off
cliffs or something.
So mostly by train.
Okay. Here we go.
This was another quote,
excuse me, "We're all dying.
Cancer patients just
have more information."
And there may be some comedy
in that, a little dark humor,
I know, but it's true.
You've got all the
information in the world.
You've got every test in the
world coming at you and saying,
"You can expect to
live this long.
This percentage, you've got
all these stats coming at you."
It's like, "Okay.
I can -- ."
It's the first time
in your life,
and your only time
probably ever,
you'll have that much insight
into your own mortality.
And here's some healing bowls
where they're dinging
in the sides.
They call her the
camel whisperer.
This camel had some issues from
being mistreated in the past.
She was calming it down.
The castle on the right
was 3,500 years old
when Alexander the Great
unsuccessfully attacked it.
Just to give you
perspective timewise here.
We're just here for
a short journey.
And whatever we can do to make
that journey more worthwhile
or extend the journey, make
a positive impact on others,
I think that's the
name of the game.
Okay. Food.
I'm in the ENT's office
mid-treatment, I'm emaciated,
a total stick figure,
can't consume enough
to sustain weight.
She receives the nurses
records, she's reviewing them
and showing substantial
weight loss plus the current
medications I'm on.
First question, "All right.
Who prescribed the marijuana?"
I said, "Well, Dr. so and
so, but he asked me not
to broadcast that fact.
I insisted on it.
It was my idea.
I was feeling that an
appetite stimulant might help."
She's a short-statured
woman, but 100% no nonsense.
She looks me in the
eye, points directly
at me, she's up like this.
She says, "I want
to see proteins,
I want to see carbohydrates,
I want to see fats."
So she was trying to, in
her way, fatten me up.
[inaudible] stage.
We didn't -- yeah.
Okay. Okay, now, my thoughts
on exploitation of elephants
for tourist purposes
have evolved since this.
I wouldn't do it again.
But they do, in fact, like
being covered with chalk,
and European girls rubbing
their noses and whatnot.
It's calming for them.
Here are the kids at
the end of it all.
Okay. It's 2017, it's
the little guy's turn.
We go to Iceland.
My first trip back to Iceland
since the Chernobyl days.
Blue Lagoon.
Yes, that military
cargo plane that crashed
on a black sand beach in 1973.
One of my yoga instructors
said to me
that you enter life
taking a breath,
and you leave life
breathing, or breath out.
And so everything in
between is really a gift.
Here's the little guy
with the waterfall.
[inaudible] there's [inaudible].
Okay. Thank you very much.
Let's just end on a quote here.
Do not regret growing older.
It's a privilege denied to many.
And thank you for extending
my life and helping me out.
I appreciate it.
[ Applause ]
>> Sandra Charles: Our
panelists are making their way
up to the podium.
And John will join them.
[ Inaudible Speakers ]
So we've had quite a morning.
And I think I delivered
on my pledge.
You've been stimulated,
informed, entertained.
And, really, it's been revealed
to you just what an
integral part each
of the people represented
here play
in this whole journey,
this whole Moonshot.
This is trajectory that we
are taking to overcome cancer.
Time for questions and answers.
I've heard so many things.
And John sort of brings it
home, because John and Juanita
as patient advocates represent
the why in all of this.
Why are Dr. Tsang, Dr. Platz
and Dr. Bates doing
what they're doing?
And these are the why.
And so having heard that, and
having heard the full plethora
of things going on, anyone
with a burning question before
I pose one to the panel?
Questions?
Right here.
Go ahead. Sure, please.
[ Inaudible Speaker ]
>> Elizabeth Platz:
That's a great question.
Is this on?
Can you hear me?
Okay. Terrific.
If we think about ecology,
and think about survival
of a species, if you have all
of the animals being exactly the
same from a genetic perspective,
and there's something
catastrophic that happens,
all of the animals could die.
But if there's more variability
in the characteristics
of those animals, some
may die, some may live.
We actually think it's the
same thing in the cancer cells.
If they have different
telomere lengths,
they may have other changes that
are correlated, and maybe some
of those cells are more likely
to live, which is a bad thing
in the case of cancer,
versus those
that are more likely to die.
And so we think it's
related to that.
And I should, I guess,
be clear when I talked
about telomere shortening
and chromosomal instability,
why is chromosomal
instability important
in the context of cancer?
Well, when you have
chromosomal instability,
there's also higher chances
of there being crossing over,
exchanges of pieces of DNA,
which then increases the risk
of cancer becoming
even more aggressive.
So we think it's
probably a marker.
It may be involved in the
cancer process, but, certainly,
it's marking just more
aggressive subsets of cells.
Now, the stromal cell, a
shorter telomere length,
that's an interesting question,
too, because it turns out that
that relationship
was independent
of the cancer cell relationship.
Together they give
us information,
even more information
than either one alone.
But when we look separately
at the variability in length
in the cancer cells and at the
length in the stromal cells,
they both provided
independent information.
So what is a hallmark
of an aging cell
that maybe a senescence?
Shorter telomeres.
Well, what is it about
senescence stromal cells,
for example, senescence
fibroblasts
that may influence
cancer progression?
Well, it turns out some
of those fibroblasts,
when they're senescent, they
change what they elaborate,
they change what they secrete.
And in some cases they
start secreting cytokines,
which ordinarily immune cells
would produce, but we're talking
about fibroblasts now.
And they might also
secrete survival factors.
And so if you have short
telomeres in the stroma
that could be related
to senescence
and this phenotype called the
senescence associated secretory
phenotype, which then
acts on those cancer cells
to make them even
more aggressive.
So it's a great question
that you asked.
Yeah. Thank you.
>> Sandra Charles: And
that sort of is underscored
by a quote attributed
to William Osler saying,
"Worry not for the
individuality of patients.
Medicine is merely a
science and not an art."
And that is, an art.
I saw another question
back here.
Barbara?
[ Inaudible Speaker ]
>> Elizabeth Platz:
I'll take this one,
too, if that's all right.
So for many years we had a field
called nutritional epidemiology,
where we tried to
identify individual foods,
individual nutrients, and
sometimes food patterns,
that are associated either with
an increased risk of cancer, or,
more importantly, protection
against the development
of cancer.
And I think we've come
to a point where we think
about more a general
pattern of lifestyle
as being potentially beneficial,
not just for protection
against cancer, but protection
against other chronic diseases,
like cardiovascular disease.
So the general strategy
that is probably appropriate
for everyone is don't smoke.
I know that's not food,
but that's the number
one cause of cancer.
Don't smoke.
The second one is
avoid weight gain.
And if you've already
gained weight, lose weight.
So many cancers are
related to obesity.
And, certainly, there's now
emerging evidence that those
who have cancer and are gaining
weight during that timeframe --
now I know, John,
you were telling us
about massive weight loss
that you experienced,
but for some cancers that is
not the typical situation.
And so those who gain weight
just because of dietary factors,
have a higher risk
of later recurring,
even after they apparently
were cured following treatment.
So don't smoke, avoid
weight gain,
lose weight if you've
gained too much weight.
And then eat a well-balanced
diet.
And so the old story
of everything
in moderation is
probably the right answer.
Big trials that have tried
to test individual supplemental
nutrients, so selenium,
vitamin E, have failed.
Right. They haven't
protected against cancer.
Except in those who
are truly deficient.
So looking in subgroups,
every now
and then there are
patterns that are found.
But most people living
in the U.S. are replete,
they're not deficient.
So making sure that your
diet is very well balanced,
eating fruits, eating
vegetables.
You know, the logic of eating
colorful fruits and vegetables
so you get a wide
array of nutrients.
Not overdoing meat.
And, John, you said
you're a vegetarian.
There are many other
sources of protein
that are non-animal-based.
And that's absolutely
appropriate, too.
Avoid eating, basically,
empty calories.
Right? You don't
want to gain weight,
so you want to make
sure you eat foods
that are providing
nutrients, not just sugars.
>> Susan Bates: I saw
something recently, though,
that said that "junk food,"
processed food was
not good for you.
>> Elizabeth Platz: So IARC,
the International Agency
for Research on Cancer, has
concluded that a certain type
of processed food, which is
processed meat and red meat,
is supported as a risk
factor for colorectal cancer.
So it's not to say that there
aren't some specific factors
that are agreed to, but,
in general, we just want
to make sure that we
minimize the chance
that we develop cancer,
these sort of bigger picture
strategies are appropriate.
And, by the way, processed meat,
do you know what
processed meat includes?
>> Sandra Charles: Bacon.
>> Elizabeth Platz: What's that?
>> Sandra Charles: Bacon.
>> Elizabeth Platz: Bacon.
Bacon, yeah.
Lunchmeat.
Right? Nitrates, nitrites.
And then also there's some
laboratory-based evidence,
not so much human
evidence, that meats cooked
at high temperature may --
well, actually they do produce
mutagens, so that's clear
that they're mutagenic.
But it's unclear if the
amount that we typically eat
of grilled food, meats I mean,
cooked at high temperature,
whether those are
cancer risks or not.
>> Juanita Lyle: From
the patient's standpoint,
John and I both shared the
fact that I didn't smoke,
I didn't do any of the
things to get cancer.
I had a very good diet,
did all the right things,
but I got cancer anyway.
But one of the things
that, because I'm now,
from the first time that I
had cancer, 42 years ago,
stage 3 breast cancer,
one of the things
that my doctor told me is the
reason why my survivorship is
such after having
cancer four times was
because I had a good
diet, I did fitness,
I did all sorts of things.
So diet does help.
Even though you might
get cancer,
it does help your survivorship.
>> Sandra Charles: Okay.
Well, thank you.
[ Inaudible Speaker ]
>> Elizabeth Platz: Yeah,
that is a good question.
So that is an emerging
area of research.
So trying to understand how the
microbiome influences cancer
development, and
then, given cancer,
how that might influence
progression
in long-term survival.
So probably the most studied
location of the microbiome
for men and women together
is the gut microbiome.
So, again, it's an
emerging area.
We don't have consensus yet.
Typically, what's been looked
at is the variety of bacteria
that are present, as well as
sort of the general amount
of each type, or the
proportions present.
We don't have final
details, like I said,
yet for the gut microbiome
and colorectal cancer.
There's some, of course,
information on the cervix.
Right? We understand
HPV, but not bacteria.
Right? So a virus, we understand
that relationship very clearly.
But are there other
bacteria that may be present
in the [inaudible]
that relate to risk?
That's an area of study.
For men, understanding
the bacterial environment
that may influence
prostate cancer risk.
That's an area of active study.
But I'd say at this time we
don't have clear evidence
that the microbiome, in general,
is protective or
a cause of cancer.
There's great variability
in moment
to moment in one's microbiome.
And, typically, the kinds of
studies that we do that are
in large cohort-type studies,
where you might have 50,000,
100,000 people in it, we,
typically, only have the money
to measure at one point in time
to collect the right
specimens and measure once.
And, really, what you'd
want is long-term exposure,
not just in adulthood, but
perhaps earlier in life.
>> Sandra Charles: And talking
about translational medicine,
a lot of people have
translated that information
into overindulging in prebiotics
and probiotics, and a number
of different microbiome
containing foods.
So everything, again,
in moderation.
And we have to be sure that
we aren't overdoing it just
because we hear one story.
>> Elizabeth Platz:
That's right.
>> Sandra Charles: Any other
questions from the audience?
[ Inaudible Speaker ]
Please.
[ Inaudible Speaker ]
>> John Tsang: Thank you.
Yeah, that's another
good question.
So I actually visited
Watson a few years ago,
and they showed me
sort of, at that time,
the most recent progress.
And at the time, my
understanding was that they,
basically, ingested, right,
and digested I suppose, too,
knowledge-wise, a lot
of the information
in clinicaltrials.gov.
So a lot of, basically,
textural,
natural language-based
information sources.
And then they tried to develop
tools to help oncologists
to make sense of the, for
example, mutational profiles
that you saw from Susan, because
often they would get, basically,
gigantic amounts of
information for each patient,
especially those who
went through a lot
of sequencing studies and other
types of OMiCC's analysis.
So the idea is to integrate
the existing knowledge
with this individualized
information, basically.
And I think it made some
good progress at the time,
especially in terms
of reducing --
sort of shrink the space through
which the oncologist had to look
through in terms
of the information.
Right? But I think the
major challenge remains,
which is that a lot of
those gene mutations,
and also expression profiles --
and we don't have much
information out there yet.
So drawing on existing databases
and existing publications
on what these complex
profiles could mean,
it's through a daunting
challenge, basically.
And especially in terms
of combining them,
because you may look at one
mutation and look at a couple
of mutations, and
you can say, "Well,
this looks like it
may predict this."
But together, how they
all give you information
on how the patient will do in
terms of therapy and response
to therapies, it's still
very difficult, basically.
So I think we need a
lot more data, in a way,
to start to discover
some of the associations,
starting with associations,
and then eventually getting to,
hopefully, causation as well.
Yeah.
>> Susan Bates: And I would
just add one thing to that.
That was a very good
answer actually for that.
The problem with the
mutation profiles is
that it's quite variable.
One cancer type will
have anywhere
from 20 mutations per tumor,
to another cancer type may
have 300 or even 3,000.
So when you have
that, you have to say
which of these are relevant.
And you really have a difficult
time figuring that out.
The pancreatic cancer
example I gave you
where we have a founder mutation
from the very beginning,
that's highly likely
to be important.
But it doesn't mean that
when we have a drug for it
that that will work, because by
then you've accumulated other
changes in the cancer.
Every single time
you make a discovery,
you have to validate it
in the clinic with a drug.
And so it becomes a very
time and long process.
You can make a prediction,
but then you have to be able
to target it to make
a difference.
So that's why it
should be a Moonshot.
That's a great way to think
about precision medicine,
including immunology.
>> Sandra Charles: And I wanted
to direct a question to you,
Dr. Bates, because
pancreatic cancer,
though the numbers are
swollen in terms of incidence,
it is a growing incidence
of pancreatic cancer.
And maybe, particularly for our
audience, the patient advocates,
we're getting feedback from
patients who are survivors.
How can we help in terms
of improving the database
that you have to do some of
the research that you're doing
with pancreatic cancer?
What things can help and
maybe stimulate funding
of that $50,000?
>> Susan Bates: Exactly.
That's a really good question.
I mean, I think it's
important for patients
of pancreatic cancer to try
to go on clinical trials.
That's been something of
a challenge, because many
of the -- I showed you
two lines of therapy.
What we don't have is a
third line of therapy.
So patients will be still fit
enough for a new treatment
at the end of the two
lines of treatment,
and we don't have one.
So that's the point
in which we need more
and different clinical trials.
But it's difficult to get
patients onto clinical trials.
There's a movement to try
to improve the eligibility
criteria,
to decrease how tight it is.
>> Sandra Charles: Right.
>> Susan Bates: Many
patients have problems
with liver test abnormalities,
or they were getting a
treatment just last week,
and don't really want to wait
six weeks to go on the next one.
So there needs to be more
work done to make it easier
to get cancer patients of all
types, but, in particular,
pancreatic cancer
on clinical trials.
You need to be able to pick
up the phone, and have them
on a trial the next week.
That's a huge unmet need.
>> Sandra Charles: Is
there any ongoing work
at any level to enhance that?
>> Susan Bates: To?
>> Sandra Charles:
To get patients
into these clinical trials?
>> Susan Bates: Yeah.
I mean, well, there are
clinical trials everywhere.
>> Sandra Charles: But in terms
of bringing them in, and --
>> Susan Bates: Yeah.
>> Sandra Charles: Informing
the community at large?
>> Susan Bates: I mean, NCI has
developed a lot of platforms
where you can search
for clinical trials,
clinicaltrials.gov --
>> Sandra Charles: Right.
>> Susan Bates: Has
gotten very good.
And I actually tell patients
to start looking at it,
start lining up what
we're going to do next.
That would really
be the best thing.
I think that information
is out there.
It just requires some
energy to come up with it.
>> Sandra Charles: Yes.
I've been struck by just reading
about translation medicine.
And it struck me that what
you said about immunotherapy,
because, of course,
that is a thing now.
Immunotherapy's supposed to
do it all for almost anything.
>> Susan Bates: Incorrect.
>> Sandra Charles: And clearly
that's not always the case.
And one of the things I
was reading also was from,
I think it was the
Microbiology Society,
which said we're
doing all of this
with translational medicine, but
we cannot forget basic science.
We cannot forget those
foundational pieces
that lead you to
do the research.
And so that sort of resonated
when you made your statement
about dealing with
the small molecules
and not just with immunotherapy.
>> Susan Bates: Yeah, that is a
flaw of medicine is that we tend
to -- when something
works, it's not medicine.
It has to do with profits and it
has to do with where people --
investors don't want
to invest in failure.
So they will invest in
companies that are more likely
to make the second of the
drug that already worked,
than they are to invest
in something that's
completely unknown potential.
And if there were one
thing we could change
about the research paradigm, it
is so much driven by investors
and by pharmaceutical companies.
So that's why I showed
you that list
of ten different [inaudible] --
>> Sandra Charles: The same --
>> Susan Bates: Inhibitors.
>> Sandra Charles: Area.
>> Susan Bates: We
do not need that.
We have, I think,
four [inaudible]
FDA-approved, maybe five.
So somehow that paradigm
needs to change.
But that's virtually impossible
to keep people from investing
in what was already proven,
already proven therapies.
>> Sandra Charles: So for
any young investigators
and researchers in the
audience, you heard it.
Go ahead, please.
[ Inaudible Speaker ]
Please.
[ Inaudible Speaker ]
>> Susan Bates: You
mean radiation therapy?
>> Elizabeth Platz:
[inaudible] radiation.
Yeah. Do you want to -- sorry.
You go ahead.
>> Susan Bates: No,
I mean [inaudible].
>> Elizabeth Platz:
We'll both do it.
So I'm an epidemiologist.
So I'm not an oncologist.
I'm not a urologist.
So it depends on the
patient's situation.
So it may depend on how
many cores were positive.
So, typically, 12
cores are taken.
If only one core is positive
and only a tiny percentage
of that core is cancer,
and the morphology,
typically called
the Gleason score,
if the Gleason score is
low and the man's older,
he and his provider may decide
to do something called
active surveillance.
If the man is young,
maybe he's 50 years old,
he and the provider might
make a different decision.
That man may not want to
undergo active surveillance.
That man may want to have a
prostatectomy, with the idea
that the surgeries done
with curative intent.
If more cores are positive
and a greater proportion
of the core is positive, and
the Gleason sum is higher,
which is a poorer prognostic,
especially if that
man is an older adult
and he has many comorbidities,
that man
and the provider may together
discuss radiation therapy.
So it highly depends on
the clinical situation
of the patient, the man's own
values, and what he cares most
about for his other
aspects of his life.
So it's not is it prostatectomy
or is it radiation therapy.
There's far more that goes into
the conversation and decision.
>> Susan Bates: And there are
clinical trials currently.
They're open where you can
enroll and be randomized,
one versus the other,
or you can choose
and then the data is collected
versus patients show
undergo surgery.
>> Sandra Charles: Okay.
Please.
>> John Bauer: Is there
international sharing
of information with
other countries
who may have a different
funding paradigm for research
that you can build on?
>> Susan Bates: There's a lot
of international
sharing [inaudible] a lot
of other countries, because
they have a more centralized
healthcare system, actually
do a better job than we do
of developing clinical
paradigms that ought
to be followed for treatment.
>> Sandra Charles: Well,
one last question and we're
at the end of our program.
>> Juanita Lyle: Now, I
would just like to say
about clinical trials, the
good of clinical trials,
because I was placed in a
clinical trial back in 1977.
And there were 814 of us
women who had breast cancer.
And there is probably
less than two-thirds
of those women who
are now living.
And in that clinical trial, one
of the things that made me go
and do the clinical
trial was simply
because you're followed
so closely.
And a lot of people had the fear
of going into a clinical trial,
but it's a bigger
benefit to going
into the clinical trial rather
than just going as a patient,
taking all of the chemotherapy
and doing radiation,
because it's a powerful
situation
where you can actually
talk to your doctor
on a level that's totally
different, I think,
than if you're not
in a clinical trial,
because everything is
being tracked so closely.
So I would say for anybody
here who is in that situation,
clinical trial is a real
benefit to the patient.
>> Tomoko Steen: We
get a lot of questions
about the clinical trial
possibilities by cancer patients
at the Library of Congress.
And often the question
comes to me.
So over 30 years I was
dealing with cancer patients
as a clinical pharmacologist.
And I didn't think this
progress is coming.
And I'm so excited about the new
change and the future progress.
Thank you so much for coming.
[ Applause ]