I’m Jerry and I study the genetics of luck now what is that cancer touches us
luck now what is that cancer touches us
luck now what is that cancer touches us all your friends your family maybe you
all your friends your family maybe you
all your friends your family maybe you and we all know people who have cancer
and we all know people who have cancer
and we all know people who have cancer and should do great and do poorly and we
and should do great and do poorly and we
and should do great and do poorly and we know people who have cancer and should
know people who have cancer and should
know people who have cancer and should do terribly and they do great
do terribly and they do great
do terribly and they do great and that’s ascribe to lifestyle or
and that’s ascribe to lifestyle or
and that’s ascribe to lifestyle or strength of will or faith or often luck
strength of will or faith or often luck
strength of will or faith or often luck well what is that I think what luck is
well what is that I think what luck is
well what is that I think what luck is is just a measure of our profound gap of
is just a measure of our profound gap of
is just a measure of our profound gap of knowledge between the interaction of a
knowledge between the interaction of a
knowledge between the interaction of a person their cancer and their therapy
person their cancer and their therapy
person their cancer and their therapy and how that impacts their response so
and how that impacts their response so
and how that impacts their response so what I need to do here first is a quick
what I need to do here first is a quick
what I need to do here first is a quick like one-minute primer of cancer in
like one-minute primer of cancer in
like one-minute primer of cancer in genetics so what cancer is is the
genetics so what cancer is is the
genetics so what cancer is is the uncontrolled growth of cells now your
uncontrolled growth of cells now your
uncontrolled growth of cells now your normal cells are fantastic about knowing
normal cells are fantastic about knowing
normal cells are fantastic about knowing when to divide when to stop so if you
when to divide when to stop so if you
when to divide when to stop so if you have a break in your leg or a big gouge
have a break in your leg or a big gouge
have a break in your leg or a big gouge in your arm the cells will grow until
in your arm the cells will grow until
in your arm the cells will grow until they fill in and repair and then they’ll
they fill in and repair and then they’ll
they fill in and repair and then they’ll stop you don’t have a big you know lump
stop you don’t have a big you know lump
stop you don’t have a big you know lump growing on your arm that you have to
growing on your arm that you have to
growing on your arm that you have to drag around as your cells keep going and
drag around as your cells keep going and
drag around as your cells keep going and going and growing how that happens is
going and growing how that happens is
going and growing how that happens is there are genes that are responsible for
there are genes that are responsible for
there are genes that are responsible for turning growth on and stopping it so you
turning growth on and stopping it so you
turning growth on and stopping it so you can also imagine these how are like
can also imagine these how are like
can also imagine these how are like switches you need to grow switch goes on
switches you need to grow switch goes on
switches you need to grow switch goes on you grow enough you stop and what cancer
you grow enough you stop and what cancer
you grow enough you stop and what cancer is has mutations that basically force
is has mutations that basically force
is has mutations that basically force this switch into the on position so it
this switch into the on position so it
this switch into the on position so it grows and grows and grows and grows and
grows and grows and grows and grows and
grows and grows and grows and grows and doesn’t stop and so then it pull if
doesn’t stop and so then it pull if
doesn’t stop and so then it pull if rates it gets into bone to cause pain it
rates it gets into bone to cause pain it
rates it gets into bone to cause pain it goes into normal organs and disrupts
goes into normal organs and disrupts
goes into normal organs and disrupts their functions all the problems with
their functions all the problems with
their functions all the problems with cancer so I study will Kimia which is a
cancer so I study will Kimia which is a
cancer so I study will Kimia which is a cancer of the blood forming organ and
cancer of the blood forming organ and
cancer of the blood forming organ and the slides that I’ve shown here it’s
the slides that I’ve shown here it’s
the slides that I’ve shown here it’s just an example for I’m talking about
just an example for I’m talking about
just an example for I’m talking about uncontrolled growth on the left is a
uncontrolled growth on the left is a
uncontrolled growth on the left is a normal bone marrow and all I want you
normal bone marrow and all I want you
normal bone marrow and all I want you get out of that is that there are
get out of that is that there are
get out of that is that there are different kinds of cells you can get
different kinds of cells you can get
different kinds of cells you can get that by the colors and their space and
that by the colors and their space and
that by the colors and their space and on the right there’s leukemia which is
on the right there’s leukemia which is
on the right there’s leukemia which is just a
just a
just a a sheet of similar leukemia cells as
a sheet of similar leukemia cells as
a sheet of similar leukemia cells as overwhelmed everything and so if I had
overwhelmed everything and so if I had
overwhelmed everything and so if I had well Kimia if I went to the emergency
well Kimia if I went to the emergency
well Kimia if I went to the emergency room because I was sick with leukemia I
room because I was sick with leukemia I
room because I was sick with leukemia I would have tens to hundreds of billions
would have tens to hundreds of billions
would have tens to hundreds of billions of leukemia cells at the time of
of leukemia cells at the time of
of leukemia cells at the time of diagnosis and so I have to get therapy
diagnosis and so I have to get therapy
diagnosis and so I have to get therapy now while I study will Kimia what I’m
now while I study will Kimia what I’m
now while I study will Kimia what I’m gonna talk about next really applies to
gonna talk about next really applies to
gonna talk about next really applies to all kinds of cancers
all kinds of cancers
all kinds of cancers there are basically three responses to
there are basically three responses to
there are basically three responses to therapy that you can have and if one
therapy that you can have and if one
therapy that you can have and if one slide can depict an entire career this
slide can depict an entire career this
slide can depict an entire career this slide is my career which is I this shows
slide is my career which is I this shows
slide is my career which is I this shows immense focus or it’s just kind of sad
immense focus or it’s just kind of sad
immense focus or it’s just kind of sad you can you can you can you can decide
you can you can you can you can decide
you can you can you can you can decide so you can have three treatment
so you can have three treatment
so you can have three treatment responses and unfortunately you don’t
responses and unfortunately you don’t
responses and unfortunately you don’t get to decide the physicians really
get to decide the physicians really
get to decide the physicians really don’t get to decide your cancer is the
don’t get to decide your cancer is the
don’t get to decide your cancer is the one making that decision right and
one making that decision right and
one making that decision right and unfortunately as physicians we’re not
unfortunately as physicians we’re not
unfortunately as physicians we’re not very well equipped to tell you which
very well equipped to tell you which
very well equipped to tell you which pathway that your cancer is going to go
pathway that your cancer is going to go
pathway that your cancer is going to go on so the first which is you get
on so the first which is you get
on so the first which is you get chemotherapy and your disease just
chemotherapy and your disease just
chemotherapy and your disease just dissolves and you’re cured that’s what
dissolves and you’re cured that’s what
dissolves and you’re cured that’s what we want there’s the second where you get
we want there’s the second where you get
we want there’s the second where you get chemotherapy and it doesn’t do anything
chemotherapy and it doesn’t do anything
chemotherapy and it doesn’t do anything we call that refractory disease in this
we call that refractory disease in this
we call that refractory disease in this case we’ve exposed patients to
case we’ve exposed patients to
case we’ve exposed patients to chemotherapy and also toxicity without
chemotherapy and also toxicity without
chemotherapy and also toxicity without any benefit at all the third is the most
any benefit at all the third is the most
any benefit at all the third is the most common you initially respond to therapy
common you initially respond to therapy
common you initially respond to therapy and then your disease comes back and it
and then your disease comes back and it
and then your disease comes back and it often comes back differently than the
often comes back differently than the
often comes back differently than the original disease it’s often close faster
original disease it’s often close faster
original disease it’s often close faster it often is less sensitive chemotherapy
it often is less sensitive chemotherapy
it often is less sensitive chemotherapy and you can imagine how devastating this
and you can imagine how devastating this
and you can imagine how devastating this is to patients who’ve initially respond
is to patients who’ve initially respond
is to patients who’ve initially respond and now they’ve relapsed they lost their
and now they’ve relapsed they lost their
and now they’ve relapsed they lost their real chance to be cured it’s a it’s a
real chance to be cured it’s a it’s a
real chance to be cured it’s a it’s a horrible thing to happen but this is
horrible thing to happen but this is
horrible thing to happen but this is still despite all of our amazing
still despite all of our amazing
still despite all of our amazing progress we’ve made in cancers this is
progress we’ve made in cancers this is
progress we’ve made in cancers this is still the major problem in all cancer is
still the major problem in all cancer is
still the major problem in all cancer is the problem of relapse so if it’s been
the problem of relapse so if it’s been
the problem of relapse so if it’s been the major problem for years and years
the major problem for years and years
the major problem for years and years and years which is still a major problem
and years which is still a major problem
and years which is still a major problem it suggests that maybe we have to start
it suggests that maybe we have to start
it suggests that maybe we have to start thinking differently about what it is to
thinking differently about what it is to
thinking differently about what it is to cure cancer what we really need to do
cure cancer what we really need to do
cure cancer what we really need to do how we think about cancer
how we think about cancer
how we think about cancer resistance so when I started doing this
resistance so when I started doing this
resistance so when I started doing this almost three decades ago the number of
almost three decades ago the number of
almost three decades ago the number of genes that were responsible for causing
genes that were responsible for causing
genes that were responsible for causing cancer you can put on one hand now we
cancer you can put on one hand now we
cancer you can put on one hand now we know that there are scores of genes that
know that there are scores of genes that
know that there are scores of genes that can cause cancer and we know that not
can cause cancer and we know that not
can cause cancer and we know that not just one mutation in one gene causes
just one mutation in one gene causes
just one mutation in one gene causes cancer a cell actually has to get a
cancer a cell actually has to get a
cancer a cell actually has to get a number of mutations and that’s
number of mutations and that’s
number of mutations and that’s presumably because these functions in
presumably because these functions in
presumably because these functions in the cell are so important that you have
the cell are so important that you have
the cell are so important that you have backups so one mutation alone doesn’t do
backups so one mutation alone doesn’t do
backups so one mutation alone doesn’t do it it takes multiple mutations to
it it takes multiple mutations to
it it takes multiple mutations to eliminate the backups to get cancer so
eliminate the backups to get cancer so
eliminate the backups to get cancer so in this mom I’ve shown here I don’t know
in this mom I’ve shown here I don’t know
in this mom I’ve shown here I don’t know far left is a normal cell and then it
far left is a normal cell and then it
far left is a normal cell and then it gets one mutation that’s that’s kind of
gets one mutation that’s that’s kind of
gets one mutation that’s that’s kind of pinkish color that’s still going to be
pinkish color that’s still going to be
pinkish color that’s still going to be behaving as a normal cell it gets a
behaving as a normal cell it gets a
behaving as a normal cell it gets a second mutation and in this model it
second mutation and in this model it
second mutation and in this model it takes three mutations into cancer and in
takes three mutations into cancer and in
takes three mutations into cancer and in Mosul Kimmy as it takes somewhere
Mosul Kimmy as it takes somewhere
Mosul Kimmy as it takes somewhere between three to five mutations with
between three to five mutations with
between three to five mutations with that you get the uncontrolled
that you get the uncontrolled
that you get the uncontrolled proliferation of cells all genetically
proliferation of cells all genetically
proliferation of cells all genetically identical to the original cancer so it’s
identical to the original cancer so it’s
identical to the original cancer so it’s almost like the cancer the Xerox machine
almost like the cancer the Xerox machine
almost like the cancer the Xerox machine is going to preserve so for those of you
is going to preserve so for those of you
is going to preserve so for those of you who are very young and I’ve never seen a
who are very young and I’ve never seen a
who are very young and I’ve never seen a Xerox machine ask the person next to you
Xerox machine ask the person next to you
Xerox machine ask the person next to you I just realize that kind of dates me
I just realize that kind of dates me
I just realize that kind of dates me quite a bit doesn’t so you basically
quite a bit doesn’t so you basically
quite a bit doesn’t so you basically have the thought is that you have
have the thought is that you have
have the thought is that you have billions of identical cells now when
billions of identical cells now when
billions of identical cells now when cells are identical to each other we
cells are identical to each other we
cells are identical to each other we call them a clone for you and lingo
call them a clone for you and lingo
call them a clone for you and lingo there and so it’s cancer is seen was
there and so it’s cancer is seen was
there and so it’s cancer is seen was seen as kind of a monolith of
seen as kind of a monolith of
seen as kind of a monolith of genetically identical cells it takes
genetically identical cells it takes
genetically identical cells it takes over now that model fits some of those
over now that model fits some of those
over now that model fits some of those three curves I showed if your cancer are
three curves I showed if your cancer are
three curves I showed if your cancer are all composed of genetically identical
all composed of genetically identical
all composed of genetically identical cells that behave the same and they
cells that behave the same and they
cells that behave the same and they happen to be sensitive to chemotherapy
happen to be sensitive to chemotherapy
happen to be sensitive to chemotherapy you give the therapy and melts away okay
you give the therapy and melts away okay
you give the therapy and melts away okay that fits on the contrary if you just
that fits on the contrary if you just
that fits on the contrary if you just happen to have a huge clone of identical
happen to have a huge clone of identical
happen to have a huge clone of identical cells that’s resistant then you give
cells that’s resistant then you give
cells that’s resistant then you give therapy and none of those cells respond
therapy and none of those cells respond
therapy and none of those cells respond okay that fits as well where it doesn’t
okay that fits as well where it doesn’t
okay that fits as well where it doesn’t fit
fit
fit is the most common that response and
is the most common that response and
is the most common that response and then relapse because if they’re all the
then relapse because if they’re all the
then relapse because if they’re all the same cells why would that happen why do
same cells why would that happen why do
same cells why would that happen why do they learn resistance all right that
they learn resistance all right that
they learn resistance all right that doesn’t make any sense so the question
doesn’t make any sense so the question
doesn’t make any sense so the question is is have we been thinking about cancer
is is have we been thinking about cancer
is is have we been thinking about cancer with that one ear model I showed wrong
with that one ear model I showed wrong
with that one ear model I showed wrong and it appears so just recently we’ve
and it appears so just recently we’ve
and it appears so just recently we’ve found that in fact cancer is not one
found that in fact cancer is not one
found that in fact cancer is not one clone it’s actually many many clones so
clone it’s actually many many clones so
clone it’s actually many many clones so you get a cancer and then you start
you get a cancer and then you start
you get a cancer and then you start having offspring which are genetically
having offspring which are genetically
having offspring which are genetically similar but different and so you can
similar but different and so you can
similar but different and so you can imagine building sort of a family tree
imagine building sort of a family tree
imagine building sort of a family tree well you have a parent cancer and then
well you have a parent cancer and then
well you have a parent cancer and then all of these offsprings as they
all of these offsprings as they
all of these offsprings as they accumulate more and different mutations
accumulate more and different mutations
accumulate more and different mutations now because of this you have many
now because of this you have many
now because of this you have many different clones different sizes they
different clones different sizes they
different clones different sizes they grow at different rates and they’re
grow at different rates and they’re
grow at different rates and they’re responsive to different chemo therapies
responsive to different chemo therapies
responsive to different chemo therapies differently many different clones that
differently many different clones that
differently many different clones that behave differently you start getting any
behave differently you start getting any
behave differently you start getting any into kind of Darwinian space survival of
into kind of Darwinian space survival of
into kind of Darwinian space survival of the fittest natural selection because
the fittest natural selection because
the fittest natural selection because you can imagine now you have a very
you can imagine now you have a very
you can imagine now you have a very complicated ecosystem of cancer it’s not
complicated ecosystem of cancer it’s not
complicated ecosystem of cancer it’s not just your normal cells versus cancer
just your normal cells versus cancer
just your normal cells versus cancer cells there’s a fight in the cancer
cells there’s a fight in the cancer
cells there’s a fight in the cancer cells itself so you have basically
cells itself so you have basically
cells itself so you have basically competition going on within the cancer
competition going on within the cancer
competition going on within the cancer and the competition between the cancer
and the competition between the cancer
and the competition between the cancer different clones and the normal is for
different clones and the normal is for
different clones and the normal is for space it’s for resources you have a
space it’s for resources you have a
space it’s for resources you have a situation of Darwinian selection now on
situation of Darwinian selection now on
situation of Darwinian selection now on the left here I show a kind of a tree
the left here I show a kind of a tree
the left here I show a kind of a tree lineage diagram of a case where someone
lineage diagram of a case where someone
lineage diagram of a case where someone had kidney cancer and used the genetic
had kidney cancer and used the genetic
had kidney cancer and used the genetic analysis of that then they had multiple
analysis of that then they had multiple
analysis of that then they had multiple metastases and you do the genetic
metastases and you do the genetic
metastases and you do the genetic analysis of all of those and you see and
analysis of all of those and you see and
analysis of all of those and you see and kind of get a family tree of how they
kind of get a family tree of how they
kind of get a family tree of how they related the long stalk there is a print
related the long stalk there is a print
related the long stalk there is a print those are the offspring so if this
those are the offspring so if this
those are the offspring so if this cancer went to ancestry.com this is what
cancer went to ancestry.com this is what
cancer went to ancestry.com this is what it would see
now I think we’re onto something because
now I think we’re onto something because look at the the branching diagram on the
look at the the branching diagram on the
look at the the branching diagram on the right looks a lot like the one on the
right looks a lot like the one on the
right looks a lot like the one on the left the one on the right is from
left the one on the right is from
left the one on the right is from Darwin’s notebook when he was trying to
Darwin’s notebook when he was trying to
Darwin’s notebook when he was trying to figure out evolution by studying finches
figure out evolution by studying finches
figure out evolution by studying finches in the Galapagos look pretty darn
in the Galapagos look pretty darn
in the Galapagos look pretty darn similar right what a thing I love is
similar right what a thing I love is
similar right what a thing I love is this little highlighted area here this
this little highlighted area here this
this little highlighted area here this is in Darwin’s notebook I think it’s
is in Darwin’s notebook I think it’s
is in Darwin’s notebook I think it’s sort of like I think I have the most
sort of like I think I have the most
sort of like I think I have the most exciting biological thought in the last
exciting biological thought in the last
exciting biological thought in the last 2,000 years and I think he’s right
2,000 years and I think he’s right
2,000 years and I think he’s right because I think this is actually how you
because I think this is actually how you
because I think this is actually how you can explain much of the behavior of
can explain much of the behavior of
can explain much of the behavior of cancer and how we have to think about it
cancer and how we have to think about it
cancer and how we have to think about it to actually cure it in the future so
to actually cure it in the future so
to actually cure it in the future so let’s go back to our model now and
let’s go back to our model now and
let’s go back to our model now and instead of looking at one giant similar
instead of looking at one giant similar
instead of looking at one giant similar clone we have multiple clones so on the
clone we have multiple clones so on the
clone we have multiple clones so on the left there the the most biggest clone
left there the the most biggest clone
left there the the most biggest clone are green we’re going to call those
are green we’re going to call those
are green we’re going to call those sensitive cells to chemotherapy and so
sensitive cells to chemotherapy and so
sensitive cells to chemotherapy and so you little you have your cancer
you little you have your cancer
you little you have your cancer ecosystem there and then you give
ecosystem there and then you give
ecosystem there and then you give chemotherapy and what that chemotherapy
chemotherapy and what that chemotherapy
chemotherapy and what that chemotherapy does is wipes out the most sensitive
does is wipes out the most sensitive
does is wipes out the most sensitive clone the green ones and then at the
clone the green ones and then at the
clone the green ones and then at the bottom there you see the trough you have
bottom there you see the trough you have
bottom there you see the trough you have some resistant cells left over now what
some resistant cells left over now what
some resistant cells left over now what have you done your chemotherapy is
have you done your chemotherapy is
have you done your chemotherapy is basically wiped out one group of cells
basically wiped out one group of cells
basically wiped out one group of cells that was sensitive but now the more
that was sensitive but now the more
that was sensitive but now the more resistant cells have room to grow they
resistant cells have room to grow they
resistant cells have room to grow they don’t have any competition they’ve got
don’t have any competition they’ve got
don’t have any competition they’ve got more space they’ve got more food and
more space they’ve got more food and
more space they’ve got more food and they grow and you get resistance and
they grow and you get resistance and
they grow and you get resistance and then you give more therapy or a
then you give more therapy or a
then you give more therapy or a different therapy you wipe out the next
different therapy you wipe out the next
different therapy you wipe out the next sensitive clone and the next even more
sensitive clone and the next even more
sensitive clone and the next even more resistant clone comes after that so in
resistant clone comes after that so in
resistant clone comes after that so in this case the unintended consequence of
this case the unintended consequence of
this case the unintended consequence of chemotherapy is breeding resistance so
chemotherapy is breeding resistance so
chemotherapy is breeding resistance so you in this tough situation where in
you in this tough situation where in
you in this tough situation where in some patients chemotherapy is zapping
some patients chemotherapy is zapping
some patients chemotherapy is zapping what they need in other cases it
what they need in other cases it
what they need in other cases it actually is putting the stage forward to
actually is putting the stage forward to
actually is putting the stage forward to actually doing exactly what you’d expect
actually doing exactly what you’d expect
actually doing exactly what you’d expect for resistance so in this case cancer
for resistance so in this case cancer
for resistance so in this case cancer has used natural selection against you
has used natural selection against you
has used natural selection against you now so far we’ve been studying this
now so far we’ve been studying this
now so far we’ve been studying this we’ve done some remarkable things but
we’ve done some remarkable things but
we’ve done some remarkable things but we’ve do
we’ve do
we’ve do you know I sort of like dude fighting
you know I sort of like dude fighting
you know I sort of like dude fighting with our hands behind our back with one
with our hands behind our back with one
with our hands behind our back with one hand because how we’d had to do these
hand because how we’d had to do these
hand because how we’d had to do these studies thus far it’s basically take
studies thus far it’s basically take
studies thus far it’s basically take millions of cells grind them up and then
millions of cells grind them up and then
millions of cells grind them up and then do your genetics in your biology on
do your genetics in your biology on
do your genetics in your biology on those so in a sense you’re averaging out
those so in a sense you’re averaging out
those so in a sense you’re averaging out all of the individual variations in the
all of the individual variations in the
all of the individual variations in the cells right so the analogy here would be
cells right so the analogy here would be
cells right so the analogy here would be akin to want to know the ecosystem of a
akin to want to know the ecosystem of a
akin to want to know the ecosystem of a swamp and so you drain the swamp
swamp and so you drain the swamp
swamp and so you drain the swamp I hear this hole and so I’ve interested
I hear this hole and so I’ve interested
I hear this hole and so I’ve interested in training swamps these days right so
in training swamps these days right so
in training swamps these days right so you drain the swamp and then you put it
you drain the swamp and then you put it
you drain the swamp and then you put it in a blender and then you do your
in a blender and then you do your
in a blender and then you do your genetic analysis right and you look and
genetic analysis right and you look and
genetic analysis right and you look and you say well it looks like there’s a lot
you say well it looks like there’s a lot
you say well it looks like there’s a lot of frog in here in this slob and it
of frog in here in this slob and it
of frog in here in this slob and it looks like that’s a bit of a duck and
looks like that’s a bit of a duck and
looks like that’s a bit of a duck and here’s a part of a lobbyist
not nice shoes and you can get useful
not nice shoes and you can get useful information out of that but not really
information out of that but not really
information out of that but not really as fine as you might like and and just
as fine as you might like and and just
as fine as you might like and and just within the last year or so we are now
within the last year or so we are now
within the last year or so we are now able to do genetic analysis and
able to do genetic analysis and
able to do genetic analysis and functional noses on single cells so you
functional noses on single cells so you
functional noses on single cells so you can actually get much more information
can actually get much more information
can actually get much more information potentially because you can actually
potentially because you can actually
potentially because you can actually take a sample divide it into each single
take a sample divide it into each single
take a sample divide it into each single cell and understand what did she
cell and understand what did she
cell and understand what did she actually that single cell is and get an
actually that single cell is and get an
actually that single cell is and get an idea about how those cells might be
idea about how those cells might be
idea about how those cells might be functioning and interacting with other
functioning and interacting with other
functioning and interacting with other cells so you get a much more depth of
cells so you get a much more depth of
cells so you get a much more depth of understanding of what this cancer
understanding of what this cancer
understanding of what this cancer ecosystem is and again we’re very very
ecosystem is and again we’re very very
ecosystem is and again we’re very very early on this and this is really in its
early on this and this is really in its
early on this and this is really in its infancy but I think this has a huge
infancy but I think this has a huge
infancy but I think this has a huge potential in driving our understanding
potential in driving our understanding
potential in driving our understanding of the complex ecosystem of cancer now
of the complex ecosystem of cancer now
of the complex ecosystem of cancer now there are huge questions we just
there are huge questions we just
there are huge questions we just beginning this you know most ideas are
beginning this you know most ideas are
beginning this you know most ideas are wrong they something might be – one
wrong they something might be – one
wrong they something might be – one question is how do you measure the
question is how do you measure the
question is how do you measure the clonal diversity of the tree you can
clonal diversity of the tree you can
clonal diversity of the tree you can make those tree diagrams but how do you
make those tree diagrams but how do you
make those tree diagrams but how do you what does it mean that one looks more
what does it mean that one looks more
what does it mean that one looks more compeiied than the other and how does
compeiied than the other and how does
compeiied than the other and how does that map to how people respond that’s
that map to how people respond that’s
that map to how people respond that’s going to take a lot of work our similar
going to take a lot of work our similar
going to take a lot of work our similar trees differently you can imagine the
trees differently you can imagine the
trees differently you can imagine the clonal structures being the same but
clonal structures being the same but
clonal structures being the same but there are different genes involved in
there are different genes involved in
there are different genes involved in each tree are those going to behave the
each tree are those going to behave the
each tree are those going to behave the same or they behave differently how do
same or they behave differently how do
same or they behave differently how do clones compete is it just a matter of
clones compete is it just a matter of
clones compete is it just a matter of you glow as fast as possible for the
you glow as fast as possible for the
you glow as fast as possible for the space you have in the resources or do
space you have in the resources or do
space you have in the resources or do actually some clones produce substances
actually some clones produce substances
actually some clones produce substances that actually impact the growth of other
that actually impact the growth of other
that actually impact the growth of other clones is there an active competition
clones is there an active competition
clones is there an active competition going on how do clones cooperate in
going on how do clones cooperate in
going on how do clones cooperate in almost all complicated ecosystems some
almost all complicated ecosystems some
almost all complicated ecosystems some groups cooperate how did these cooperate
groups cooperate how did these cooperate
groups cooperate how did these cooperate it’s curious that in the leukemia if you
it’s curious that in the leukemia if you
it’s curious that in the leukemia if you use really really sensitive techniques
use really really sensitive techniques
use really really sensitive techniques we can find like one leukemia cell there
we can find like one leukemia cell there
we can find like one leukemia cell there background by a million normal cells
background by a million normal cells
background by a million normal cells there’s many cases where patients will
there’s many cases where patients will
there’s many cases where patients will be cured for ten years and have a very
be cured for ten years and have a very
be cured for ten years and have a very very small amount of they will Kimia
very small amount of they will Kimia
very small amount of they will Kimia that still persists and it persists over
that still persists and it persists over
that still persists and it persists over years and they don’t realize that’s
years and they don’t realize that’s
years and they don’t realize that’s called dormancy and we don’t understand
called dormancy and we don’t understand
called dormancy and we don’t understand what that is
what that is
what that is but one thing you might imagine if you
but one thing you might imagine if you
but one thing you might imagine if you believe this model and said that’s a
believe this model and said that’s a
believe this model and said that’s a clone of cells that without helper cells
clone of cells that without helper cells
clone of cells that without helper cells without cells that you’ve illuminate
without cells that you’ve illuminate
without cells that you’ve illuminate with you chemotherapy they can’t grow so
with you chemotherapy they can’t grow so
with you chemotherapy they can’t grow so they’re just going to sit around forever
they’re just going to sit around forever
they’re just going to sit around forever and really not cause a problem and in
and really not cause a problem and in
and really not cause a problem and in fact they just might take up some space
fact they just might take up some space
fact they just might take up some space and prevent more variant clones from
and prevent more variant clones from
and prevent more variant clones from growing and I think the most important
growing and I think the most important
growing and I think the most important thing is do we need to kill all the
thing is do we need to kill all the
thing is do we need to kill all the cancer cells to cure people if I have a
cancer cells to cure people if I have a
cancer cells to cure people if I have a thousand billion leukemia cells can I
thousand billion leukemia cells can I
thousand billion leukemia cells can I actually cure that with chemotherapy
actually cure that with chemotherapy
actually cure that with chemotherapy that might be mathematically impossible
that might be mathematically impossible
that might be mathematically impossible to do but if you understand dude the
to do but if you understand dude the
to do but if you understand dude the ecosystem enough and how these things
ecosystem enough and how these things
ecosystem enough and how these things interact with each other maybe you could
interact with each other maybe you could
interact with each other maybe you could do much more targeted therapy eliminate
do much more targeted therapy eliminate
do much more targeted therapy eliminate the clones you need to and not need to
the clones you need to and not need to
the clones you need to and not need to keep pounding on chemotherapy and people
keep pounding on chemotherapy and people
keep pounding on chemotherapy and people at a point where it doesn’t do any good
at a point where it doesn’t do any good
at a point where it doesn’t do any good and just causes toxicity so I think in
and just causes toxicity so I think in
and just causes toxicity so I think in the future we know now what we think the
the future we know now what we think the
the future we know now what we think the rules of the game are Darwinian
rules of the game are Darwinian
rules of the game are Darwinian selection okay that’s an old friend and
selection okay that’s an old friend and
selection okay that’s an old friend and what we want to try to do is make it so
what we want to try to do is make it so
what we want to try to do is make it so that natural selection is working for us
that natural selection is working for us
that natural selection is working for us instead of against us so I think when
instead of against us so I think when
instead of against us so I think when people walk in the door with the disease
people walk in the door with the disease
people walk in the door with the disease we’ll be able to fairly quickly decide
we’ll be able to fairly quickly decide
we’ll be able to fairly quickly decide whether or not they’re on that one
whether or not they’re on that one
whether or not they’re on that one completely refractory pathway or not and
completely refractory pathway or not and
completely refractory pathway or not and if that’s their going to be their fate
if that’s their going to be their fate
if that’s their going to be their fate it’s got to think outside of the box
it’s got to think outside of the box
it’s got to think outside of the box about biological differences between
about biological differences between
about biological differences between those and the other cells use some new
those and the other cells use some new
those and the other cells use some new type of therapy to get them into a
type of therapy to get them into a
type of therapy to get them into a therapy response curve once you’ve given
therapy response curve once you’ve given
therapy response curve once you’ve given therapy and the cells are going down
therapy and the cells are going down
therapy and the cells are going down rather than just let them go back up
rather than just let them go back up
rather than just let them go back up we’re gonna actually use this as a to
we’re gonna actually use this as a to
we’re gonna actually use this as a to our advantage we’re gonna use this as a
our advantage we’re gonna use this as a
our advantage we’re gonna use this as a trap so we’re going to kill all the
trap so we’re going to kill all the
trap so we’re going to kill all the cells that we can that are sensitive and
cells that we can that are sensitive and
cells that we can that are sensitive and when then the ones that are left over
when then the ones that are left over
when then the ones that are left over will actually study those cells find out
will actually study those cells find out
will actually study those cells find out what’s left over and what they’re going
what’s left over and what they’re going
what’s left over and what they’re going to be sensitive to and then from that
to be sensitive to and then from that
to be sensitive to and then from that point on manipulate eliminate clones
point on manipulate eliminate clones
point on manipulate eliminate clones that we know can be very much clones
that we know can be very much clones
that we know can be very much clones that aren’t going to do any harm you let
that aren’t going to do any harm you let
that aren’t going to do any harm you let them live this is going to be
them live this is going to be
them live this is going to be complicated natural selection evolution
complicated natural selection evolution
complicated natural selection evolution has a several billion year head start on
has a several billion year head start on
has a several billion year head start on us humans trying to figure it out
us humans trying to figure it out
us humans trying to figure it out but I think that in the end this is
but I think that in the end this is
but I think that in the end this is going to be a game where we can actually
going to be a game where we can actually
going to be a game where we can actually change luck we can take those patients
change luck we can take those patients
change luck we can take those patients who are going to relapse and have bad
who are going to relapse and have bad
who are going to relapse and have bad luck and do things so that we make them
luck and do things so that we make them
luck and do things so that we make them into patients who have responded have
into patients who have responded have
into patients who have responded have good luck and doing that will be greater
good luck and doing that will be greater
good luck and doing that will be greater than how we’re treating cancer today
than how we’re treating cancer today
than how we’re treating cancer today Thanks
Thanks
Thanks [Applause]
”
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