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Dr. Brian Druker: “Anatomy of a Breakthrough in Targeted Cancer Treatments” | Talks at Google

Dr. Brian Druker: “Anatomy of a Breakthrough in Targeted Cancer Treatments” | Talks at Google


[APPLAUSE] BRIAN DRUKER: Well
thank you, Vic. And thank you for hosting me to
visit my first visit to Google. And I hope it’s not my last. What I want to do in my talk
is not really focus on science. And what I really
want to talk about is, how did I get
to do what I did? And it wasn’t like I woke
up some day and said, I’m going to cure cancer. The reality is,
is that there were lots of steps and lots
of processes and lots of things had to
fall into place. And as I look back,
I can try and dissect some of those things. And you can apply
success in any field to success in any other field. And so I hope what I’m
talking about are, maybe, some life lessons,
maybe some things that you probably already know. And I’m just telling you
what you already know. So I’m just going to
take you through some of those steps, step by
step, of some of the things that I’ve learned about what
had to come together for me to go from a laboratory
to a clinical project and, ultimately,
success in patients. So the first lesson is,
breakthroughs take time. As I said, you don’t wake
up some morning and some aha moment and you’re all done. And there’s oftentimes a
very, very lengthy process. And the best way
I can convince you that breakthroughs take time
is to try to transport you back 100 years. Let’s go back 100 years. Early 1900s– life expectancy
in the United States is about 47 years. And the leading cause of
death in the United States are infections. Pneumonia, tuberculosis,
diarrheal diseases– infectious diseases
are the leading cause of death in our country. But you go forward a
century, and pneumonia, influenza– they make
headlines now when a new infection comes along. When Ebola comes along,
it makes headlines. HIV, in the ’80s,
made headlines, because these are
new infections. And they were frightening. But by and large, we don’t
worry in our daily lives about infectious diseases. We worry about heart
disease, cancer. You know, when you think about
interactions with your doctor, it’s, you go to your doctor. You’ve got cancer. Will I ever get cured? And those are the kinds of
interactions that we have. So what happened over the
course of the last century? What breakthroughs
occurred to lead to the state of affairs we have
with infectious disease, where we think of many of them
eradicated, many of them treatable? And I think it’s, like,
1903– we actually started doing sewage treatment,
chlorination of water, pasteurization of milk. In the 1940s, we put
refrigerators in our houses. So these are the things we
take for granted that make our food and water supply safe. 1940s– antibiotics. If you had said to somebody,
I’m going to specifically target bacterial infections,
in 1900, they would have thought
you were crazy or came from a different planet. So it wasn’t until the 1940s
that penicillin came along. And then the 1950s– vaccines. Polio vaccine was 1955. Smallpox was eradicated. And now in the news, it’s people
aren’t getting vaccinated. It’s in the news. So we know vaccines work. But if you recast that,
that’s prevention. That’s specific treatments. And that’s modulating
the immune system. So I could go through all
of these breakthroughs. But again, this is a
century of progress against infectious disease. So breakthroughs
certainly take time. Now the disease I
worked on– called chronic myeloid
leukemia– started with its first
description in 1845. We understood the
cause by about 1985. And by 2001, we had
a specific therapy. So that’s the timeline for
the disease I worked on. The other thing that’s
important about this is, this is what I call my
translational research slide. You describe a clinical entity. You understand it. And then you can actually
do something about it. So clinical description of CML. 1845, two pathologists–
Bennett and Virchow– describe the autopsy findings
of patients with leukemia. Now, let’s go back to 1845. No microscopes. They did this based
on autopsy findings. And then they submitted these
articles for publication. And thereafter ensued
a rancorous debate about who was really
first, because these were published within
six weeks of one another. So debates about
priority– nothing new. But think about
publishing in 1845. And some of you in this
audience have probably grown up in a generation where
there haven’t been computers. In 1845, there weren’t
even typewriters. And just to give you an idea of
what the current generation is growing up with– my
daughter is eight years old, my youngest daughter. And she just recently achieved
a black belt in taekwondo. And as a reward, she wanted
me to buy her a typewriter so she could type out old
fashioned Google Docs. That was her impression
of the world. She has not lived in a
world without Google. But 1845, these
two were typeset, submitted somehow to some
central place for review, and ultimately
they got published. And in a public
lecture, Virchow said that Bennett had described
his case six weeks before. So Bennett gets
credit for first. So fast forward about 150 years. And the disease I worked on
called chronic myeloid leukemia is one of the four
common types of leukemia, making up about 15% to
20% of all leukemias. There are about one to two
cases per 100,000 per year. That translates roughly to
about 5,000 new patients per year in the United States. And that number 5,000 will
be important in a little bit. The disease can
affect any age group. But the average age of onset
is somewhere between 50 to 60. And historically, people lived
about three to five years. You got diagnosed. You went to the doctor. The doctor said, you’ve
got three to five years. And that was pretty much it. OK. So now, back to lessons learned. If we’re going to do
anything about this disease, we need to understand it. So breakthroughs
require knowledge. You have to
actually– hopefully, you have to understand
what you need to do. Breakthroughs require knowledge. So if we’re going to intervene
on chronic myeloid leukemia, we need to understand
what drives the growth of this leukemia. And here, we have two
pathologists again. Peter Nowell, David Hungerford–
working in Philadelphia in 1960– described
an abnormal chromosome in the blood and bone
marrow of patients with CML. And they published
this landmark article in the journal “Science”
which, for those of you not in the science field, this is
the most prestigious journal in all of scientific literature. This is the entire article–
three paragraphs long. That’s right. Quality and quantity
do not equate. But when you publish
a scientific article, in your last paragraph you
get to wax philosophically about the broad implications
of your findings. And what they said
were, “The findings–” this abnormal
chromosome– “suggest a causal relationship between
the chromosome abnormality observed and [INAUDIBLE]
it was called chronic granulocytic leukemia. Now, turns out they
were absolutely right. But in 1960, nobody
believed them. The general view was, this is
some associated abnormality. It has nothing to
do with the cause. But they were absolutely right. So next lesson–
breakthroughs often occur when different fields
of investigation converge. And currently, there’s a
lot of emphasis on what’s called conversion science. But you also have
to realize you have to apply the right technology
to the right problem at the right time. Now when I started
out in the lab, if you could sequence an
entire gene, that was huge. And it would take you
weeks, if not months, to do one whole gene sequence. Today we talk about,
how many genomes can we sequence in how short
a period of time? So if I wanted to talk about
whole genome sequencing 20 years ago, that
would have been crazy. So the reality
is, you have to do the right technology
at the right time based on where you are. And that’s part of the reason
breakthroughs take time. In the case of CML,
there were three threads that came together– three
critically important threads. The field of tumor
virology was started in and around the early
1900s with Peyton Rous at Rockefeller University. Led to the oncogene field,
broke open by Bishop and Varmus at UCSF. And that led to
the molecular cause of chronic myeloid
leukemia, this fusion gene called BCR-ABL. Abel There was an entire field
of chromosome analysis that identified this short
chromosome in the patients with CML that lets you map genes
to chromosome locations that allowed people to realize that
two genes had broke apart, joined together, and created
this abnormal fusion gene. And this entire field of
protein phosphorylation– a post-translational
modification of proteins– that put phosphate onto
specific residues– tyrosine kinase–
putting phosphate onto tyrosine residuee– allowed
you to begin to think about, could you develop
a specific therapy for this molecular abnormality? So I got into this
field right around ’85, when all these things
were coming together. And I looked at– I was
working on kinase at the time and thought, here’s a disease
I know is caused by kinase. I should be working on it. And maybe I can move
us this direction. So another thing I
want to talk about is, breakthroughs require
seeing things differently. Now, everyone says, oh. You’ve got to think
outside the box. Well, I want to
get you to think, sometimes the answer is
staring you right in the face. And you can’t see it. So I’m going to an audience
participation exercise. So get ready. I’m going to put a sentence up. And the rules are, I want you
to read this sentence from start to finish, once through. And as you’re reading
this sentence, count the number of Fs. OK? Everybody ready? OK. Let’s see how we did. How many people didn’t–
raise your hands. How many people
didn’t see any Fs? How many people saw one? How many people saw two? How many people saw three? How many people saw four? How many people saw five? How many people saw six? How many people saw seven? How many people saw
more than seven? OK. Same rules. Read it through one more
time, start to finish. OK. Since I’ve– how many
people saw one F. Two? Three? Four? Five? Six? Seven? OK. Go ahead and count. Six. We all read the same sentence. And the answer was
right in front of us. Now, there are
lots of reasons why this occurs this way,
because lots of people drop the Fs in of. But the reality is,
sometimes the answer is right in front of you. And you just have to
see it for what it is. I’m going to give you a couple
of real life examples of where that has happened– one
non-medical and one medical. I’m going to start with Velcro. So Velcro– really
useful invention. Turns out this guy, George de
Mestral– a Swiss engineer– was hiking through the woods
one day with his velvet vest on and his dog, and comes back. And his velvet vest–
just covered with burrs. Now, how many millions of
people have gone on hikes, come back with their
clothes covered with burrs, picked the things
off their clothes, had some choice words
for it, and then went on with their business? Well, George said, why
do these things stick so tightly to my velvet vest? He asked the critical
question– why? Turns out he had a microscope
down in his basement. So he went down. And he saw that
his vest had loops. The burrs had hooks. And he said, I bet I could
make a fastener out of that. So again, something that
anybody could have seen was right in front of him. And he made it into
something useful. Alexander Fleming– a lot of
people have heard the story. He walks into a lab, sees
that his plate of bacteria are contaminated with yeast,
and instead of throwing it out like millions of people
have done, including myself, he looks at it a little bit
more carefully and says, oh. Isn’t that interesting. The bacteria aren’t
growing very well around the yeast contamination. Maybe I should track that down. Well, the back story
of Alexander Fleming is that he is or was a surgeon. He had spent a fair
bit of his time during World War I
growing frustrated at taking bullets out
of wounded soldiers, only to have them die of
infections several weeks later. So he dedicated his career
to identifying specific ways of killing bacteria. And about 12 years after he
had started in the laboratory, was the fateful day that he
walked into the laboratory and saw that contaminated
plate of bacteria. So again, the answer was
right in front of somebody. But they needed to
see what was there. So I got into the field
around 1988, 1990. And here is where the field was. For CML, we had this
abnormal chromosome called the Philadelphia
chromosome, because that’s Nowell and Hungerford worked. It’s present in virtually
every single patient with CML. We knew from animal models
if you put this oncogene into mice, they get leukemia. And we know that it functions
as an activated intracellular kinase. And one of the first laboratory
experiments I did was I made a mutation in this kinase–
made it kinase inactive– and it didn’t work. So I saw this as pretty
simple, straightforward. Shut this thing down. Specific therapy. The rest of the
world thought, oh. It’s a much more
complicated disease. It’s not a simple disease
caused by one gene. And targeting this
probably won’t work. So the way I looked at it
was, this is how kinases work, over there on the left. Kinases bind ATP. They transfer phosphate in
a case of tyrosine kinases to tyrosine residues
on proteins. And it’s these tyrosine
phosphorylated proteins that cause white cells
to grow uncontrollably. So I thought, you
shut that down and you have a specific,
targeted therapy for CML. It turns out that there
were a couple of companies. One was Novartis. It used to be Ciba-Geigy. And Nick Lydon was
my colleague there. We had worked together. His company’s group at
Novartis had synthesized a handful of drugs that
seemed to shut down a variety of kinases. And in 1993, they sent me a
handful of their compounds for testing. And my lab showed that this
one, which ultimately turned into Imatinib or Gleevec,
was the best of the drugs that they had sent
me at, specifically, killing CML cells. Now, it should have
been really simple. We had a drug. We had laboratory data. But there were lots and lots
of reasons this drug never should have been developed. First of all, the
prevailing view was you could never make
a drug against a kinase. The prevailing view in the
world was, I just showed you something that binds ATP. Well, in the genome, there are
at least 500 to 1,000 proteins that bind ATP. And the view was, ATP is ATP. You shut down one, you’re
going to shut down all of them. And why would you ever
try to make a drug to hit one or two or three
of these family of proteins. So the view was, its just never
going to be a viable target. So don’t even bother. The next was we’re oncologists. And oncologists, notoriously,
are a pretty pessimistic bunch. And the view was, when has
a single drug in oncology ever worked? So why would you ever go after
a single target in oncology? And then even biochemists
looked at this and said, well, you’re never
going to swamp out ATP. So why bother with
that, as well. So we had all the oncologists
against and all the biochemists against us. And then, we had the
problem of toxicity. So even if we could get a drug
against a couple of kinases, the view was the early knockout
mice of individual kinases were embryonic lethal. So even if you shut
down one kinase, the view was, you’re
going to kill people. And that’s not a drug we
ever want to take a risk on. But the biggest hurdle
from the drug industry– 5,000 patients a year. How will you ever
make enough money to justify its development? So if you think about
this, the prevailing wisdom is it costs somewhere between
$500 million to $1 billion to develop a drug
from pre-clinical on through marketing. And one in 10 drugs succeed. So if your market
size is 5,000 a year, market projections were about
$100 million a year and a 1 in 10 chance of success. So if anyone wants to invest
a billion dollars for a return on investment of
$100 million a year and a one in 10 chance of
success, please let me know. We have lots of ideas for how
you can invest those funds. But the view was, this
would just not make enough. Now, it turns out everything
was wrong on this slide. And it said, we need to
develop a successful drug. You just need one patient
to develop till you’ve got a successful drug. And this was my one patient. And this is a before
and after picture. Now, this is Imatinib and after. Now, the reason I have these
numbers is the patient’s wife was an accountant. She likes numbers. She likes charts and graphs. She’d come into clinic when her
husband’s white count was high. And she said, Dr.
Drukar, you’re not doing very well at controlling
my husband’s blood counts, are you? And I’d say, sheepishly, Ma’am,
I’m doing the very best I can. And I’d change his dose
of meditation around. And I’d usually overshoot. He’d bottom out. We’d back down. His counts would go up. And we had this seesawing
pattern of his blood counts. In April of ’99, we started him
on Imatinib at 300 milligrams per day. And by December of
that year, she said, Dr. Drukar, you’re
actually doing pretty well. I’m going to stop
checking up on you. Now, the FDA doesn’t
like anecdotes. And nor do I. But the reality
is, in 2 and 1/2 years from the first patient
on our clinical trial, we got FDA approval. And it was one of the
fastest FDA approvals in the history of
the FDA, and still is the fastest from the
time the drug company submitted the portfolio to
the approval of this drug. And in 2001, it appeared on the
cover of Time magazine with, is this the breakthrough
we’ve been waiting for? So where are we now? So fast forward eight years. We do a very large
randomized trial. And I’m just showing you
the Imatinib or Gleevec arm. Now remember–
three to five year life expectancy was
historical, here. Now, with Imatinib,
95% five year survival. And these curves are holding up
out to 10 years and 11 years, still running about a
90% 10 year survival. So, completely changed the
course of this leukemia. And as Vic said, we
have taken what was once a fatal or lethal
leukemia and turned it into a manageable condition. But the reality
is, there are lots of people who are benefiting. And let me just share
one story with you. [VIDEO PLAYBACK] -Hello, everyone. My name is Katie. And I’m very excited
to be here tonight. I’m going to start
out by telling you all a little bit about myself. I’m 18 years old. I’m a nursing student at
University of Portland. I graduated in the top 8%
of my high school class. I was– [APPLAUSE] Thank you. I was part of the Royal
Crowns Dance Team, where I was team captain,
all state athlete, and state champion. I love my dogs, Italian
food, and “Gray’s Anatomy.” And when I was six years
old, I was diagnosed with chronic myeloid leukemia. We all know what happens in a
treatment for cancer– chemo and radiation, hair
loss and nausea. But would you like
to know a secret? I never had any of that. I had Gleevec. Because of Brian Druker, my life
is as I described it to you. Dr. Druker began
developing Gleevec the same year that I was born. And it was FDA approved just one
month before I was diagnosed. And if you want to
talk about timing, that’s some of the best
that I’ve ever heard. It’s because of the
Knight Cancer Institute that this timing is possible. It’s because of the
Knight Cancer Institute that Dr. Druker
was able to develop this groundbreaking new drug. It’s because of Brian that I got
to carry a first-place trophy back to my dance team at state. And it’s because of the
Knight Cancer Institute that I’m going to school
to become a nurse. Can you imagine a world where
cancer is merely a memory? Brian Druker, Phil
Knight, and you together are making this a reality. And I personally thank you. [END VIDEO PLAYBACK] BRIAN DRUKER: So
there are hundreds of other stories, thousands
of other stories like this. And it’s certainly
extremely gratifying to see these things happening. But the reality is that
this served very much as the groundwork for
all of what we’re hearing in personalized cancer therapy. It’s about matching patients
with the right therapy at the right time. And it started with Herceptin. It started with Gleevec. It started with many of
these other drugs that showed oncologists
that we actually can develop successful
treatments based on the knowledge of what
drives the growth of cancer. So where else has
Gleevec worked? And it’s worked in about a
dozen different diseases Vic mentioned, the most
prominent of which are gastrointestinal
stromal tumor, a relatively uncommon intestinal tumor. About 2 or 3% of melanomas
have a target for Gleevec, and a couple of other rare
skin and blood diseases. So what lessons have we
learned that we can now apply to other drugs? And I hope I’ve convinced
you a little bit that you have to understand
what you’re doing. You need to have a good target. And if you have a good
target and a good drug, you really can get good results. Now, I’ve used this slide
for many, many years. And as you can tell, I’ve put a
lot of emphasis on the target. But recently, I’ve been reminded
by a couple of near drug failures that you
also need a good drug. And there have been a couple
of examples, recently, where there are some
really good targets. And the one example I’d
use is BRAF and melanoma. There are a couple of
drugs that came out that were called RAF inhibitors. But they weren’t very good. They didn’t work in
metastatic melanoma. And then people said, oh. It must be the target. When other companies
came in with really good mutant BRAF drugs, 60% to 80%
response rate and some pretty good durability. So bad drugs almost
killed good targets. So I have to balance
this equation. Need both sides– good
drugs, good targets. And you can get good results. So if we’re going to translate
the success of Gleevec to other cancers,
we have to start by getting the right targets. These are going to be the early
changes that cause the tumor. But we have to treat early
in the course of the disease. If we use Gleevec for
early stage disease, it works really well. If we get patients at much more
advanced disease, it works. But people more likely
become resistant. So to do that, we have to
develop reliable techniques for early detection. And these aren’t going to be
things that will detect things that don’t need treatment. These are things that
actually need treatment because we may deploy
some toxic therapies. And we have to smart
about what we’re doing, getting the right
patient the right drug. So if you have the
right drug like Gleevec, we know what disease
it will work for. We know what diseases it won’t. We can be smarter about
patient stratification. So where are we now? We’re still, in cancer, in
this kind of empirical world where we treat cancer because
it’s breast cancer, lung cancer, colon cancer. We use a lot of
empiric treatments. And a lot of them
are pretty toxic. And we never know who’s going
to respond and who won’t. And we just can’t predict
what’s going to happen. But that’s changing. And with precision
medicine, we’re headed toward an era
where we understand what’s driving the growth of
each and every cancer and we treat based
on that knowledge. And it doesn’t matter if you
have prostate cancer, breast cancer, or lung cancer. We treat based on the target. It’s much like a mechanic
lifting up the hood of a car and seeing there’s an engine in
whatever kind of car you drive. And the same parts will break. And we base the treatments
on knowledge– information. And the treatments can and
will work the first time. They’re going to be far more
effective and far less toxic. And if you look at the spectrum
of lung cancer, at least over half of the mutations in
lung cancer are already known. And 10 years ago, my
colleagues in lung cancer were the most pessimistic bunch. But now, lung cancer
is the poster child for precision medicine in
all of oncology because of this knowledge
driving the way that treatments are deployed. But in addition, as I said,
deploying the right technology at the right time, what
an amazing opportunity we have with the ability
to interrogate tumors. We can do whole
genome sequencing. We can do expression profiles. We can understand
metabolomics, proteomics. And you guys here can put
all this together and tell us in the clinic what
to do about it. That’s really exciting to me
because this is all happening. And it’s happening now. And it’s allowing us to use
precision treatments based on knowledge, not
just empiricism. So I talked to you about
where we were a century ago. And what do I see
for this century? And I see us taking a very
similar broad-based approach to cancer, as we did
for infectious diseases in the last century. And although I’ve
focused a lot of my talk on specific therapies
directed at critical targets, that’s sort of like
saying antibiotics are going to be all we
need for infections. We know we need more. We know we need to
understand and harness the power of the immune system. And I’m really pleased
with what’s happening here. Despite the fact that I’ve
had this slide in my deck for over a decade
and it’s been really hard to point to any success
in the immune therapy, now there are real successes. There are half a
dozen different drugs targeting the ability
of the immune system to kill cancer that are working. And they’re working
incredibly well. But in addition, we have
to think about prevention and early diagnosis. Now the reality is
that, for every $1,000 we spend on the first two,
we’re spending about $1 on these last– prevention,
early detection. And in my view, even
though my own institution is doing a lot of work in the
specific therapies because of our leadership
position– I worry a lot that we’re not doing
enough in the prevention and early detection. So because of that, I started
to put together a plan. And I started to seek investors. And if you know the
landscape of Oregon, there’s one real
billionaire– Phil Knight, co-founder of Nike. And my institution,
cancer institution, bears his name because
of a $100 million donation he gave us about
six or seven years ago. So we began to put
together a plan. We went back to Mr.
Knight and his family and talked about what
we might want to do. And to set this up,
about a year and a half ago we held an event. He and his wife were
the honorary co-chairs. For those of you that know Phil
Knight, he’s incredibly shy. He doesn’t like public speaking. The only way I got him
to show up was to say, you don’t have to say a word. A week in advance, he
called me and said, is it OK if I introduce you? Well, of course it’s
OK if you introduce me. Is anything I can
do to help you? Do you need my bio? No, no, no. I’ll just say a few things. So nobody in the
audience had any clue what he was going to
say, including me. But this is what he said. [VIDEO PLAYBACK] -As I speak, there is a
grandfather, a mother, a child who hugs
a loved one, hugs a loved one he or she
would not be able to hug if it were not for Brian Druker. It is incumbent on
everyone in this room to do what he can to
keep the miracles coming. And I speak to myself, as well
as to all of the rest of you. Accordingly, I make
the following pledge. Penny and I will
donate $500 million to OHSU if it is
matched in pledges within two years in a
fundraising campaign. If the campaign
raises 499 million, we are relieved of our pledge. If it raises 500
million or 10 billion, our donation will
be 500 million. Is there a higher calling
than curing cancer? [END VIDEO PLAYBACK] BRIAN DRUKER: So, two years,
500 million, all or nothing. To give you a little
bit of context here, my cancer center has raised five
or 10 million in a good year. So, seemingly impossible feat. But here’s where we are
with about 10 months to go– 482 million raised,
including 200 from the state. This 200 from the state
for buildings counts. Over time, we’ll replace that. So it’s about a $1.2
billion investment. Now what’s remarkable
about the state was, when we went to the state it
was, isn’t this what you wanted your state to be known for? Aren’t these the kinds
of job that you want? And it was passed 85 to five. Republicans, Democrats
agreed on something. We’ve gone out to the
business community. They’ve gotten behind it. We’ve gone to the
labor community. They’ve gotten behind it. They had a campaign called
Unite for the Knight. We’ve had donors
from all 50 states. We’ve had bake sales. We’ve had $50 donors. We’ve had hundred
million dollar donors. But people have
rallied behind this. And they have put us close. But as Mr. knight said, 499,
we don’t get anything from him. So we have to get
to that finish line. So you know, and I’m
talking to Google. And a billion dollars
might seem like not a lot. But for academics, a
billion dollars is a ton. And so what we
want to do, though, is we want to do
something differently. We want to stop being
a bunch of academics working on disparate projects. We want to make an impact. And so we want to
think about, how can we make an impact by putting
together a team of people and focus them on a problem? So in a very short order,
we want to assemble a team. We want to focus them. We don’t want them spending
all their time writing grants. We want them to focus
on solving a problem. We want to equip them well,
get them the right tools so they can actually
focus on the work. We want them to work as a team. And I know, again, at
a place like Google, teamwork seems so obvious. But in academics, we
don’t incentivize it. We incentivize people to do
individual parts of a puzzle and hope it works out some day. Why don’t we work as a
team, focus on a problem, and solve the problem instead
of making the problem, how are you going to get
your next grant or how or what are you
going to publish? And we want to be
open and sharing. If there are people
around the world, around the country
that can help us, we want to work with
people that can help us. If some of the money needs
to go outside of Oregon because somebody doesn’t want
to move there, we can do that. We want to solve a problem. And in addition,
we’re going to have to train a whole
bunch of people, because we don’t think
the workforce exists to do this work today. But we want this
work to be sustained. So it’s an ambitious plan. We’re just getting
started on that. We’re planning our buildings. Were beginning to recruit people
as we close in on our goal. But along the way, we’ve
actually had some fun. So this is Gert Boyle,
Columbia Sportswear. And she had this ad
campaign several decades ago where she put her son
under ice or throw snow at him with a snow bulldozer. And she was called
one tough mother. Gert– actually, I
worked with her sister as an undergraduate
at UC San Diego. And Gert donated $100
million to our campaign. So we put together this
thank you campaign with her. But more importantly,
what Gert did was she inspired our most
important people. And that’s our patients. This is a patient who’s
going through a bone marrow transplant for her lymphoma. And she wanted to get
on the action, too. So she’s got her one
tough patient tattoo. So we have a lot of work to do. We have a lot of promise. We have a lot of potential. We need to live up to that. But I’m confident
we can do that. And in closing, the people
I really want to thank are the patients who went
on this journey with me. These are people
who had been told, get your affairs in order. You may have less than
six months to live. And they found their way
to our clinical trials. And they’re still here today,
doing things they enjoy. This is a picture of the longest
continuous patient on Gleevec. She is now 16 and a half years
from taking her last family trip because she
thought she wasn’t going to be around much longer. First patient from Italy
doing things he loves, which is dancing. Patients spending time
with their grandchildren. And this is actually
a 14-year-old picture. She now has two
great-grandchildren from the two older
children on this picture. Lots of people who traveled to
Oregon for our clinical trials. And some people doing some
absolutely remarkable things. This is a photo of a woman
who came to Oregon in 2000, was the first patient from
Australia treated with Gleevec. She went back to
Sydney and was one of the torch bearers for the
Sydney Olympic games in 2000. So individual people,
individual success. But it all starts to add up. And so, we can take
one disease at a time, one person at a time. And it all starts to add up. And this is my picture of
hope, my hope for the future that we see lots more
pictures like this of people surviving and thriving
despite a diagnosis of cancer. Thank you very much. MALE SPEAKER: And Brian,
maybe first I can ask, every generation–
every 10 years or so– there is
a war on cancer, a battle declared on cancer. Each generation
has its own reasons to be optimistic about new
scientific developments, things that happen in allied fields. And I know you mentioned
a bit about this. But perhaps you
could tell us why you are particularly
optimistic this time that, not a cure for
cancer, but at least management of cancer
as a chronic condition is within reach. BRIAN DRUKER: So I
don’t know how much of “The Emperor of All
Maladies” you’ll show or you people have watched. But it’s so different than
it was 20, 30 years ago when I started out. And we had no knowledge
of what we were doing. It was all empiric. And when we think about hope,
to me this is real hope. And when you see rapid,
dramatic responses because of an understanding of a
cancer, as opposed to something that you have no clue what,
how, or why it will work, and we really– to
me, it’s a matter of unraveling this puzzle. And so I think that, actually,
it’s a very different feel. When I have lung
cancer doctors who are optimistic about
what they can do or melanoma doctors
or the New York Times has an article about kidney
cancer doctors having five drugs they can use, when
five years ago they had none, and oncologists are even
becoming optimistic– when that happens, there
has to be some real hope. And again, I just think we’re
taking a completely different approach by understanding
sort of these three pillars. In the past it’s always
been, we’ve got to kill it. We’ve got to kill it. We’ve got to kill it. And now it’s, we’ve got to–
yes, we have to kill it. But we have to kill
it more intelligently. We have to bring in
the immune system. And then we have to think
about moving up more early. And so it’s always knowledge
driving it as opposed to this empiric, maybe we’ll
just combine the right drugs and get lucky. MALE SPEAKER: Sure. And I do think,
in this audience, most people will be familiar
with the new tools that are generating new information
about the molecular basis of cancer and the new ontology
of the diseases resulting. Let’s talk about the other
two things that you mentioned. One– you called it the
other side of the equation. Let’s start with that first. I wonder if you could tell
us about some new tools and techniques for manipulating
cancer, manipulating the tumor environment, including
the immunotherapies. BRIAN DRUKER: So, one of the
things that we’re understanding about cancer is that cancer
isn’t just this isolated tumor that grows on its own. And it’s surrounded by
lots of immune cells. It has a micro environment. But the best
analogy I ever heard was, I was talking
about this to a guy by the name of
Wayne Drinkward who owns a construction company. And he’s a really bright guy. And he said, oh yeah. I got and I do accident
assessments at my site. And sometimes it’s a bad
worker, and sometimes the bad environment that causes
all of my workplace accidents. So cancer isn’t any different. Sometimes you’ll get
a bad seed driving the growth of the cancer. But sometimes it’s the
soil around the cancer or the inability of the immune
system to attack and target it. And understanding cancer’s
three dimensional system using either organized, growing
in better, reproducible mouse systems, allows us to
do better interrogation of what’s driving the growth of
the cancer and what might work and what might not. MALE SPEAKER: So,
a related question. I mean, we’ve known since
before the time of aims that there are some
environmental factors which cause cancer. We also now know of many genetic
factors, many genetic lesions which predispose one to cancer. Looking at an audience like
this, how would you say– how would you think about the
genetic risk for cancer? What causes cancer? And how do you think
about environmental risk? How has that changed with
these new tools and techniques? BRIAN DRUKER: Well, I
may give a longer answer. So bear with me. MALE SPEAKER: Please. BRIAN DRUKER: First I
want to make a pitch for, we have to continue to recognize
that we need to get people not to start smoking or to stop. It’s still the number one
cause of cancer deaths in our country. But why is smoking so lethal? And it’s lethal for two reasons. First of all, it
directly damages DNA. And second of all, it
injures lung tissue. So it causes the cells to grow. So it’s a double hit. It causes your cell to grow. And when they grow,
the DNA gets damaged. That causes mutations. They’re going to drive cancer. But that gives you a window
into other environmental causes. Chronic inflammation that causes
cells to grow more predisposes to cancer. Things that damage DNA–
going to predispose to cancer. People born with BRCA defects
that can’t repair DNA mutations are more predisposed. So we can begin to get an
insight into predispositions, both genetically from–
clearly, all of us carry some predispositions,
genetically. You overlay that upon
environmental factors, either through exposure
to infections, exposure to things that
cause inflammation. We actually can take
the same paradigm and move it back and
say, if we understand what our predispositions
are, either genetically or, at some point in time,
we see some reaction that causes some inflammation, we
actually begin to get targets. So instead of this
broad-based vitamin C, vitamin E– pick your
favorite vitamin, or something is going to
lower your chance of cancer. We’re going to be able to
actually go and target and say, if you take this medication
for this period of time, we’ll lower your risk of cancer. And we’ll do it in
a more precise way. I don’t think we’re
quite ready for that, other than in very
well-defined conditions. MALE SPEAKER: Sure. BRIAN DRUKER: But we have
the tools to understand that by doing sequencing, doing
it again, and monitoring large cohorts of people to
see what their outcomes are. MALE SPEAKER: So you
evoked inflammation, again. And I want to return
to the question about the immune response and
modulating the immune response. But do you see the
modulation of inflammation, in a generic sense, as a viable
chemo prevention strategy? BRIAN DRUKER: I’m certainly
open to considering general immune modulation as a
potential for decreasing cancer risk. Part of that’s going to
mean, how safe are the drugs? Or would you look at
high risk populations? Given a window, if you
see some inflammation, could you decrease that? Or in people, certainly,
with chronic inflammatory conditions– we know that, for
example, chronic pancreatitis is one of the highest risk
factors for pancreatic cancer. Now, there’s a target
population where, if you wanted to decrease
the risk of a deadly disease, that would be a population
where I would think you could run a clinical trial. And we know that ulcerative
colitis– Crohn’s disease– very high risk of colon cancer. And depending on where you are
on the course of that disease, a colectomy may be a
recommended course of treatment. I think we can do
better than that. MALE SPEAKER: Right. BRIAN DRUKER: And similarly
with BRCA1, BRCA2, we recommend some pretty
significant surgeries– mastectomies, oophorectomy. Could we think of a
medical intervention? And again, if you start
to extrapolate that all on that spectrum, we’ll get to,
still, high risk conditions. If we come up with the right
genetic framework that say, we might be able
to target somebody, or if they have an inflammatory
condition on top of that, maybe we intervene. And I’ll give you
one more example of an investigator who’s looking
at postpartum breast cancer. Really, very highly lethal
form of breast cancer. And it has to do with the
change of the breasts that occur when women are
pregnant and then either breastfeed or don’t, and
the changes occur there. There may be a
window where you can use an anti-inflammatory
that would lower the risk of getting that
lethal form of breast cancer. So we have, already,
lots of clues there. MALE SPEAKER: Interesting. And if there are any questions,
please just stand up. Philip? The slide which
showed four hurdles in the development of
Gleevec, and he asks you to dive deep into one of them. BRIAN DRUKER: Yeah. So, one of the more
interesting stories was there were some animal
toxicity with Gleevec in the early animal
studies in rats and dogs. And I looked at the way the
study was done and thought, well, wait a second. We give a therapy to people. We give toxic
chemotherapy to people. And as an oncologist, I’m
not afraid of a little bit of toxicity. And if I see some liver enzymes
going up, we stop the drug. That doesn’t concern me. But the people at the company
were really worried about that. They didn’t want to do anything. And because of the way
the company was set up, they couldn’t go and talk to
the FDA to ask their advice. So I called up the FDA. And I said, here’s
the toxicity package. What do you think? Oh, my goodness. That’s more than we usually see. Why don’t you send it through? So I called the company back,
told them what I had done. And they were really
upset with me. And nobody does this. This is not the way
we do things here. But it was enough to get them
to consider that, maybe, we could actually get
this through the FDA to start a clinical trial. And the other story
I’ll tell is– and how did I finally
convince the company? And for years, I would
approach the company when one of my
patients would die. And I’d say, why don’t you
go into clinical trials? And what I realize now, that–
I didn’t have kids at the time. And [INAUDIBLE] have kids. I still am struck by the
fact when I ask my kids, what do you want for dinner? I don’t know. What do we got? And then I say, well, would
you like pizza or hamburger? They’ll make a decision. Or they may say, I
don’t want either one. But at least they’ll
make a decision. They’ll make a choice. And when I say to the
drug– what I learned was, people aren’t actually
any different than kids. They’re just more grown up. But they still make
decisions the same way. And we give them an
open-ended question. Why don’t you develop this drug? I don’t know. We don’t want to. Then when I gave
them a choice, and I worked with Nick Lydon, who
had actually now gone to a spin out company– and said,
would you develop this drug in a limited phase one trial
or would you license it out to Nick and me? Now they’ve got a choice. Now they can take it to a board. And they can say, which
one do you want to do? And they decided, we want to
run our own limited scale phase one because if it works, we
want all the royalties and all the income off the drug. So they made a choice. So a really simple sort of aha
moment that, 20 years later, I realized I did the right
thing by giving them a choice. MALE SPEAKER: It’s interesting,
just to follow up on that. I mean, you’re of course
famous for your perseverance over these
bureaucratic obstacles. Has the environment in oncology
drug development changed? Or do we still face many
of the same obstacles? BRIAN DRUKER: I sort of divide
the world into those that get it and those that don’t. There are some companies
that are completely on board. And some companies are still
stuck back 20 years ago and are looking at
how much money we’re going to make as opposed to,
can we get this through quickly? Can we get to the
market and then expand? And Gleevec– I don’t get
any royalties on Gleevec. It was already patented
when it came into my lab against any tumor in
a warm blooded mammal. So there was nothing I was
going to add to that patent. And Novartis’s revenue was $4
billion last year on Gleevec. So they completely
mis-estimated, underestimated the market. And again, the point is,
if you can get something to clinic quickly
and then expand that’s, to me, the way to go. And some companies
really do get that. MALE SPEAKER: So, just
to repeat the question– Joseph’s question is about the
idiosyncratic nature of Gleevec with respect to other
targeted cancer therapies and that the
response is durable. BRIAN DRUKER: That’s
why I say we’ve got to treat early in
the course of the disease when the disease
are less complex. I don’t think we’re going to win
by targeting advanced cancer. We’re going to win by
treating it more early when it’s less
heterogeneous, when it’s more treatable, more curable. And that’s why I’m moving
a significant effort that direction, because
I’m tired of having to answer the question
like this, which is, yes. We need to get– I
think we might be OK with triple,
quadruple combinations of the right targets, shutting
down bypass mechanisms. But it’s going to
be really tough. And it’s going to take
decades to do that. At that same point, I
want to move up earlier. When the diseases looked
more like CML– because CML, in its earliest stage, is
kind of a pre-malignancy that, ultimately, will convert
to a fatal malignancy, in three to five years. If I can move the clock
back for other diseases, we can have more
treatments like this. MALE SPEAKER: What
do you think are the most impressive
new methods to study the pre-malignant to malignant
transition in cancer? BRIAN DRUKER: I wish I had
a great answer for that. I think it’s going
to require studying of the right
patient populations. And by that, I
mean a large cohort of people falling over
time to see what lesions, what abnormalities
correlate with poor outcome. I think we can accelerate that. And when I’ve talked about–
you know, Oregon, for example. Could we go and look at
every man or woman who has died of breast
or prostate cancer and ask the question why? Did we not detect their
cancer early enough? OK. Maybe that’s a reason. But if we did detect it– if
we didn’t, what do we need? What could we have detected
early that would have said, this is what we
should be detecting in these patients who are still
dying of their other cancers? And can we learn
from the people, from samples that are
already out there, as to what we should be detecting? So I think there are
certainly some early wins we might be able to get to. But what to detect,
how to detect it– that’s our next decade of work. MALE SPEAKER: Well, what
about new animal model systems or in-vitro model systems? I know we were discussing
some of this at lunch. What’s your feeling about– BRIAN DRUKER: Oh, I may be a
little controversy on this. But– MALE SPEAKER: Please. BRIAN DRUKER: My view of the
best way to study human cancer is to study humans. And I don’t think we
have great animal models. I think animal models
may be informative for certain questions about
where in the micro environment because you can’t do
those studies in people. But if you want the
genetic lesions, I think you’ve
got to get people, because they’re going to
tell you what’s happening. And we can artificially put them
into animal models and say, oh. We have a model of
pancreatic cancer. But then you’ve got to go and
validate it in people anyway. So why not just skip
that intermediate and go right to people? MALE SPEAKER: So does
your skepticism also extend to patient-derived
xenografts, organoid models, some
things that are hybrids between these approaches? BRIAN DRUKER: Patient-derived
xenografts and organoids are the things that we are
moving to in our center. And I certainly believe in
them because they allow us to recapitulate human cancer. But to come up with
an artificial model that you say looks like,
smells like, but it still isn’t human cancer–
again, I think our resources should be devoted
to study of human cancer. MALE SPEAKER: And this raises
another logical question about modeling the
immune system in animals, which of course is fraught– BRIAN DRUKER: Yeah. Right. MALE SPEAKER: So let’s
go back to the question of immunotherapies. What do you think is the
next step, beyond just checkpoint inhibition
or combinations of checkpoint inhibitors
with other things? What’s the next step in
immunomodulation and control and re-engineering, if you
will, of the immune system? BRIAN DRUKER: The
biggest issue to me is, we can’t predict who will
respond to immunotherapeutics and who won’t. And if we could
understand that, we might be able to convert
non-responders into responders, whether that be– is
it mutational burden? Is it the inability of the T
cells to infiltrate and then get activated? What is it about certain tumor
types or certain patients? In melanoma, it’s a 20%
to 30% response rate? And some of them are
incredibly durable. What about the other 60% to 70%? Why aren’t they
responding as well? So I think we need to
understand who’s who. And if we understand why, then
we might be able to convert. And to me, that’s the biggest
hurdle in immunotherapeutics right now. MALE SPEAKER: Just the
information and understanding. So, other questions? Stephanie, first. BRIAN DRUKER: I’ve
been trying to– MALE SPEAKER: Stephanie
asks you to contrast the different response rates or
the durability of the response rates in two tumors. And she asks whether
it’s a function of the stage of diagnosis. BRIAN DRUKER: So, for those
of you that don’t know just as well as– the
response rate to Imatinib with CML is a quite
durable response. And as I showed, their
survival curve 85, 90%. With gastrointestinal
stromal tumors, responses last on a median
of two to three years. And then you’ll see resistance. So the reasons for that,
I’m not entirely clear. One possibility is
that imagine Imatinib isn’t quite as potent
against the target in GIST as it is against
the target in CML. The other is, you typically are
getting the tumors a little bit later in GIST than
you do in CML. So that may kind
of tie into that. But it also comes back to
my comments about earlier. If you use adjuvant Imatinib,
for three to five years we actually are seeing
survival benefits and significant
survival benefits. So again, it may just be
the biological heterogeneity by a later detection. Or, as you catch
these tumors earlier, we may have a bigger impact. MALE SPEAKER: The question
is that many cancers may have a genetic profile that is
not targetable or even lacks a clear target or a
known driver mutation. And how can we apply the
same strategy to them? BRIAN DRUKER: So
I think about most of the common tumors that have
been sequenced in the cancer genome atlas. Most have a target. For something like
ovarian cancer, it’s almost all P53,
which we can’t target. So we may find targets. But we may not be able
to target them yet. So I can’t think– if you
know of, I can’t think of an example– AUDIENCE: I was thinking on your
slide about the lung cancer, for example, the unknown chunk– BRIAN DRUKER: Oh. Yes. Right. So the unknown chunk on
my lung cancer slide– there’s probably P53 in there. There’s RB in there. But actually, I didn’t– what I
put were known targetable with current drugs. I didn’t put– so
the reality is, we know a lot more than
what we can do today. But that’s why I didn’t–
I want to close the loop. And thank you for
allowing me to do that. 20 years ago, kinases
weren’t a druggable target. So now there are hundreds
of kinase inhibitors in trials– dozens have
been FDA approved– for an un-druggable target. So P53? Not druggable. Well, that’s today’s technology. Maybe tomorrow, somebody will
figure out how to target it. There’s a huge RAS
initiative, headed by Frank McCormick
formally of UCSF, looking at RAS, which is
one of the most commonly mutated targets across
all cancer types. We currently don’t have
a good drug for it. So just because something
is un-druggable today doesn’t mean we aren’t trying
or we won’t have one some day. MALE SPEAKER: And perhaps as we
apply more pathway-based tools to analyzing these
key signalling– BRIAN DRUKER: Exactly. MALE SPEAKER:
–systems, there will be upstream regulators or other
regulators that are targetable. BRIAN DRUKER: Exactly. MALE SPEAKER: So
related question– do you think that
the TCGA data– which is, I think, the most
comprehensive data set of its kind
available now– do you think it’s been
mined to the extent that it can be for new targets? BRIAN DRUKER: You know, it’s
an interesting question. And a group that I’ve worked
with actually mined TCA data and identified
some new chromosome translocations that
were in that database but just not recognized
because of the algorithms. So I think the answer is yes. I suspect most of the low
hanging fruit’s been mined. But there may be more
with better, more sophisticated analyses. But I think what we’re
lacking are more samples. And I think, as the
rich– you know, the reality is we’re going
to get hundreds of thousands of cancer genome sequenced,
expression profiling. I think we just need a
richer data set to– along with better algorithms. MALE SPEAKER: So
one thing that we started to discuss is how
much information you think is available just
by understanding an ensemble, the
cells in a tumor, and how much is lost
by not really having analytical techniques
that resolve, with spatial resolution,
the heterogeneity in all these measurements
within the tumor? Perhaps you can comment on that. BRIAN DRUKER: Yeah. So one of the things
that Joe Gray, who was recruited from
Lawrence Berkeley has, has a spatial systems
biomedicine initiative where he really is trying to
understand cancer as a three dimensional system– where,
for example, Herceptin lives in these filaments
on cancer cells that talk to other cancer cells. That may open up a whole new
way of looking at breast cancer and how they communicate
one to another or to their micro environment. And whether that is going
to turn into a therapeutic, I don’t know. But it’s just
fascinating new biology as we understand cancer as
a three dimensional system as opposed to looking
at it in a Petri dish. MALE SPEAKER: Yeah. I mean, it really seems,
as Weinberg suggests, that the tumor has
all the complexity of any other organ of the body. BRIAN DRUKER: Yeah. Exactly right. MALE SPEAKER: So Mark’s
question is about early detection and, specifically,
the discordant funding available for early
detection versus programs that target later stages
in the cancer story. BRIAN DRUKER: Well,
I blame two things on why there’s so much
funding for late stage cancer. The first goes back to
when I was in training and Hodgkin’s disease was cured
with four chemotherapy drugs. And the principles were
non-overlapping toxicity, different mechanism action. Combine the right four
drugs and you cure a cancer. And everybody got
on board and said, we’re going to cure cancer by
combining the right four drugs. And you got CHOP,
and you got ABBD. And you got all these
quadruple combinations. And it didn’t happen. But we had all
this funding going. And then I come along, and I
introduce a drug for a target. And everyone says, we’re
going to cure cancer with these targeted drugs. And then you get resistance. And now it’s, maybe you’ve
got to do three or four drugs. So I take some of the
blame for the fact that we’re funding so
much advanced cancer, because people got optimistic. And we forgot that for
decades– the 15 years I’ve been talking about targeted
therapies, immune modulation, and prevention, early detection. You’ve got to have those
three pillars if you’re going to make an impact. But because of the way that our
funding has gone, it’s been, here’s something
right in front of us. This patient needs something. Here’s a drug that worked. And let’s all get
on board for that. So it’s been an interesting
evolution in my own thinking that we have to do
things differently. But it’s really hard to
convince large funding agencies that you need to move. MALE SPEAKER: Talking
about the whole subject of early detection in general–
I don’t know if you’d agree. But it seems like the scientific
state of early detection is abysmal right now,
except in a few cases. You have nonspecific
markers– they may or may not be actionable– or
imaging modalities where they contrast with
respect to the pathology you’re trying to observe is minimal. So how are we going to
change this, practically? BRIAN DRUKER: I absolutely
agree that the state of the art right now in
early detection is abysmal. And there are certainly some
pockets– Stanford Canary Center just doing
some amazing work. There are a few
other places where some things are happening. But that’s why we want
to make this investment and put a stake in the ground
of, let’s get a group together and figure out how
to do this better. And if I had a blueprint for
how we’re going to do it, I’d tell you. But I don’t. I just know that we’ve
got to make an investment. We have other people
around the world. Cancer Research UK has done a
similar assessment and said, we’ve got build this field. And we want to build this. We’re going to
build this together. We’ll build it with Canary,
with Cancer Research UK and a few other
like-minded partners and train the next generation. They can actually
make an impact here. MALE SPEAKER: So let me ask a
proxy question, then, related to that. Is the holy grail for you
a multifactorial blood test or something from a
tumor biopsy sample that would help you
stratify patients, stage disease, maybe in the
blood test diagnose it earlier? Or is it a noninvasive
molecular imaging tool that could really be applied
at a population scale? Which is– or do you not know? BRIAN DRUKER: Yes. I think it’s going to be a
combination of lots of things. And so if you look at
the most effective tool for lowering the death
rate from cancer, it’s been the pap smear. MALE SPEAKER: Yes. BRIAN DRUKER: So
you know, you can imagine that, maybe
for some tumor types, you need a scraping
of, you know. Do you need a cheek swab
for head and neck cancers? Your colonoscopies–
already quite effective, but pretty invasive. Could you imagine
a stool sample that would allow you to
detect something that you might need to do a colonoscopy? Are there imaging
technologies that will let you see a
pancreatic cancer? Or is there a blood
test you’ve got to do first to narrow
the bin of people that would go through an
imaging procedure so you’re not spending all
of our healthcare dollars on screening? So I don’t think it’s going
to be a one size fits all. It’s going to be lots of–
each different tumor type may require a different technology. As a holy grail, maybe
there’s something, you know, finding from the
baseline study that says, here’s the transition
from health to disease that says you might need to
be more carefully screened. That would be a
holy grail, if you could have been a really
inexpensive screening technology that
would let you say, this is the person
that should undergo more intensive screening. But I think that’s
a long ways off because we’re going to need
large numbers of people and large long term follow up. MALE SPEAKER: And
perhaps large tumor samples or samples of the
pre-malignant state as well. BRIAN DRUKER: Exactly. MALE SPEAKER: I think there
were some other questions. Yes? I’m sorry. I don’t know your name. Joanne’s question is
about technologies that seek to interrogate,
non-specifically, the immune system through
combinatorial arrays of peptides and their
role in cancer diagnosis. BRIAN DRUKER: Yeah. And I guess we talked
about this earlier. I’d even go beyond that to
what are called theranostics, meaning, could you
attach something to an immune peptide that
would recognize an early tumor and destroy it or allow the
immune system to destroy it? So then you can get away
from this conundrum of, is it going to be lethal? Is it not? Do I need to take it out? Should I leave it in? Can I watch it? You know, maybe you can
just let the immune system get activated, take it out at
the same time it’s detecting. That would be another holy
grail of what we could identify. MALE SPEAKER: But I think
her question, specifically, is about using the immune system
as a tool for surveillance and early diagnosis of disease. BRIAN DRUKER: Great. MALE SPEAKER: And
let me add to it. Do you think that that can
be done non-specifically, in the sense that
you have a chip that exposes random epitopes? And then also, can it
be done specifically, in the sense that, can we learn
enough about tumor antigens to actually design a test
that uses the immune system to detect cancer? BRIAN DRUKER: I think
you’ve stated perfectly what needs to be done. And I certainly believe
that that can be done. MALE SPEAKER: Does Gleevec have
a role in multiple myeloma? And do you conduct
clinical trials for Gleevec or other
agents in that disease? BRIAN DRUKER: So Gleevec was
tried very briefly in myeloma. And unfortunately, it didn’t
have much benefit there. Myeloma is another
field where things are changing very rapidly. And there are lots and lots
of new agents being developed. There’s an antibody
against CD38, which is one of the cell
surface markers on myeloma that’s showing spectacular
results in clinical trials. There are several new
agents for resistant myeloma that are also showing
remarkable activity and are getting moved
up to earlier stages. We aren’t a huge myeloma center. But there are several
around the country that are, if you’re asking for a
specific person in your family, I’d be happy to help refer
it to some of these trials. MALE SPEAKER:
Let’s speak briefly on a related subject about CARP
therapies– Chimeric Antigen Receptor T cell therapies–
which, you know, has its antecedents
in Star Trek. So it’s something that
we like in this audience. But how do you feel, in
general, about the idea of re-engineering tools of the
immune system to fight cancer? BRIAN DRUKER: Well again,
the CAR-Ts are again, another example when I talk
about immune modulation of the remarkable success
of immune modulation. The concern I have
with the CAR-Ts is that there’s still a fair
bit of toxicity to them. And we need to understand
how to better utilize them in a safer manner. You know, some of my colleagues
in bone marrow transplants say, well, you know, we’re
used to bone marrow transplants and rescuing people. And we can do these
cell therapies. And I agree. We can. It’s just that, having
started out from a perspective of, how can we treat cancer
in a simpler, less toxic, less invasive fashion, I see
the results from the CAR-Ts and I like what’s happening. But I also think, how can
we do better and get them to a safer place where we can
utilize them more effectively? MALE SPEAKER: It’s
also one thing if the CAR-T therapy is an
ablative therapy against B cells, you know, where
there’s a well-defined target. But how optimistic are
you that these things can be extended to
solid tumors, where I guess it faces the
same problem that we’re discussing in the
molecular imaging context? BRIAN DRUKER: Again,
those are my concerns. If you’re taking out an
entire cell type– B cells, you can kind of live without. And you take out
some other cells that you need for
heart, lung– you know, these could be really toxic. And even as we move to
myeloid malignancies, some of my colleagues have
been unwilling to take out the myeloid lineage
because you’re going to be predisposed
to infections. So we need to
understand how best to target what the
good targets are and, maybe, how to even dial
back on some of the toxicities. MALE SPEAKER: His
question, to paraphrase, is that some argue
that Gleevec is curing the disease it treats. And then, at what point
do you stop treatment? And how do you, I
think, ethically think about doing that? BRIAN DRUKER: So about 20%,
maybe 30% of people on Gleevec will be molecularly undetectible
for the BCR-ABL transcripts. And if you stop therapy, 50%
will remain undetectable. And 50% will relapse and
need to be retreated. So it’s 50 50 of the 20 or 30%. So it’s a small percent. And we don’t know who’s who. So there are some hints
that it’s immunologic. And the hints are as follows. We know that people
who previously received interferon, which is the
prior generation of treatment for CML, have a little bit
higher chance of getting off therapy. And I’ve had patients who
I’ve taken off therapy. Their PCRs for the
BCR-ABL transcripts turned slightly positive. I’ll check again. And they’re back
to undetectible. And they bounce around
at really low level. And they’ve done that for years. So I can’t imagine– we haven’t
eliminated the last CML cell. So to me, it means there’s got
to be some immune recognition. Now, if we can take those
clues and say, what is it about the immune system that’s
being recognized on the CML cells? And can we convert
people from unable to discontinue to being
able to discontinue, then maybe we can actually get
more people to stop and get from control to cure. And that’s actually one
of the current areas of focus in my lab. MALE SPEAKER: So
in several answers, several responses,
including this one, we kind of take for granted
as a thought experiment that we’d be able to
recruit the cohorts to do these gigantic trials of
combination therapies. But the lamentable fact is
that only 3% of patients are in trials to begin
with in oncology. So how optimistic are you that
these questions can actually be answered today? BRIAN DRUKER: Yeah. So it’s lamentable that
we enroll so few people in our clinical trials. And in part, that’s an
infrastructure issue, meaning we just don’t
have enough people in the healthcare industry
to put people on trials. I don’t think it’s
a lack of interest. I think it’s just a lack of
enough manpower to do the work. So I think that’s going to
require some investments. And you know, I
didn’t go through all of our billion dollar plan. But I’m putting
about 100 million into our clinical
trials infrastructure so we can put more people on
trials at our institution. But it’s not going to get
us to the tens of thousands of people we need to actually
test with these combinations and doing them quickly. But if we can show that it
can be done at one place, maybe other places will follow. MALE SPEAKER: And
there, perhaps, there is some overlap in the
technologies one would develop for early detection
and the ones you would use for
stratification to design better powered BSCR trials and
other trials, biomarker driven. BRIAN DRUKER: And
certainly, in AMLS, the other area we’re
putting a lot of investment is, we’re doing a BSCR trial
where everybody gets screened. We have treatments
for everybody. So our idea is that
anyone with leukemia gets enrolled on
a clinical trial. And it should be 80%
of people, not 3%. MALE SPEAKER: As it
is in the childhood analog of these cases. So the question asks about a
global perspective on cancer. And how can some
of the, I assume, advanced technologies that
we’ve been discussing actually bear on the global problem? BRIAN DRUKER: Yeah. So I’m going to come back
to an earlier statement. First of all, one of the
things the US has done really well is export smoking. And so, a lot of
the cancer deaths worldwide are smoking related. And it’s not something we
should be terribly proud of. But we talk about
prevention, we have to think about how
we manage that part. As far as how we manage
advanced cancers, you know, if you look at the
paradigm in HIV, it is a really
tough road to think about managing HIV in countries
that can barely afford– they can’t afford the drugs. And so, that’s why
I think we’ve got to think about– we have
to imagine, how do we do early detection
that’s cost effective? How we do pap smears
around the world? And there are
certainly technologies that can allow us
to do that, have them read at a central location,
and can lower the death rate from cervical cancer. So there are already
programs in place that can be a leading
edge, if you will. But I think the best
way is going to be prevention and early detection. If we’re going to rely on
this safety net of treating advanced cancer, we’re going
to bankrupt entire countries by doing that. So globally, we’ve really–
to my way of thinking, this is where we
need to be moving. And it’s the same as
you think about HIV. It’s really vaccination
that’s really going to be the best
technology at making a global impact on HIV. Same with malaria
and other diseases. We’ve got to think about how
you do this cost effectively. MALE SPEAKER: So
speaking of vaccination, I think we’d be
remiss to not ask you to comment on HPV
vaccination and the controversy it’s caused, at least
in a few US states. What’s your feeling? BRIAN DRUKER: Well, my kids
have all been vaccinated, boys and girls. So I hope that speaks for
what I think about it. You know, I’m acting
in a way that I think a responsible parent should. And it’s not about, you
know– you can make it about whatever you want. But for me, it’s about
preventing cancer. And early on, I had talked,
I had thought about, do we put legislation
through in our state? And after seeing the
pushback from other states where it just didn’t
happen, I just realized we’re not going
to win this battle. But you know, I can only
speak for my own family and what my beliefs are. MALE SPEAKER: Absolutely. And I think, in that case,
it is such a clear example of chemo prevention, if
you will, that its amazing. BRIAN DRUKER: And before some
of the immunotherapeutics came along, that was
what I put in the check box of immune
modulation, was a vaccine that can prevent cancer. Now, don’t we want more of them? MALE SPEAKER: As we
develop new treatments– and I think it’s true
broadly of any treatment, including in HIV and
infectious diseases– there will be some
societies that find them objectionable
for cost or other reasons, in the case of HPV. How do we deal with that? BRIAN DRUKER: Yeah. We’ve got to engage our social
science colleagues on this. And we have to figure
out these problems. Because you know, you look
at any societal problem– it’s often as much
behavioral modification as it is anything
we can do medically. And I don’t have a
clear view on how we accomplish that,
other than we’re going to have to
face those issues. MALE SPEAKER: So in
the end, the solution might be web advertising. BRIAN DRUKER: It
very well could be. Or it could, you know,
social pressures. And you look at, you know,
how do you get people to vote? It’s did you post it
on your Facebook page? And you know, I voted. And why don’t I want
all my friends to vote? I stopped smoking. I want all my friends to stop? I got the HPV vaccine. I want all my friends to. There’s incredible pressure
with social dynamics. And we need to harness that. MALE SPEAKER: So
one last question. I think, then, we have
to start the documentary. But I know you were visiting
our colleagues at Facebook this morning. So tell us what the
responsibility and the duty of the Silicon Valley technology
industry is in this area, in early detection. And what, in your opinion,
are the unique tools, if any, that we’ve developed that could
help you with this problem? BRIAN DRUKER: So I’m going
to take two points, there. First of all, I think everyone
saw the power of philanthropy. And the reality
is, is that there is a lot that can be done with
philanthropy in moving things forward that need
to be moved forward. So I think it’s important to
recognize, you know, the people that run Google, the people that
run Facebook, are giving a lot. And that needs to be
encouraged because there are societal problems
that– and it’s not just throwing money at problems. It’s actually throwing money
at smart problems getting to solutions. But the sorts of tools
that are being created at Google, particularly in the
ability to understand biology by bringing large
amounts of data together, aggregating
large amounts of data, and then helping
us understand what that data is trying
to tell us– you know, when I started out in my
career, my first mentor said, you’ve got to let
the data tell you what it’s trying to tell you. Let the data speak for itself. And I think that’s what
Google is doing so well, is bringing all this data
together and letting it speak. And so, you can
identify patterns. You can do so well at
identifying patterns and what is the most important
because we’re going to be deluged with data. But we need to understand that. So it’s not just as
much generating it. It’s helping us figure out,
sifting through mounds of data, bringing it together,
identifying the patterns, and then saying, that’s
where we need to go. And that’s where the
tech industry can help us, is bringing
computational biology, is bringing pattern
recognition, is bringing computational algorithms. I don’t think generation of data
is our limiting factor right now. I think it’s understanding
what it’s trying to tell us. MALE SPEAKER: And please
join me in thanking Brian. BRIAN DRUKER: Thank you.

  • That's a LOT of $$ that was raised. ($1 bn).
    How much of it actually came from the public (taxes)? How much of it will actually go towards real, progressive research (with life-saving benefits)

    FYI …

    Gleevec has had serious issues:
    from t(he latest Scientific American– April 2016):

    And the drug Gleevec was hailed as an emblem of targeted cancer therapy when it shrank tumors in a subset of leukemia patients with a very specific mutation in their tumors. But then, in a lot of patients, tumors developed new mutations that made them resistant to the drug, and when they did, the cancer returned. Gleevec bought many of those patients time—a few months here, a year there—but it did not change the final outcome.*

    http://www.scientificamerican.com/article/the-paradox-of-precision-medicine/

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