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Precision Medicine When Every Cancer IS Personal | Adam Marcus | TEDxPeachtree

Precision Medicine When Every Cancer IS Personal | Adam Marcus | TEDxPeachtree


Translator: Matt Chan
Reviewer: Emma Gon Thank you,
thank you for your time here today. I want to talk a little bit
about cancer research today, which is a topic you may
or may not be interested in. I kind of want to make a wild guess,
sort of an assumption, that everyone here has somehow
been impacted by cancer. Whether it’s been a friend,
perhaps a family member, or I can guarantee you that there’re some
courageous survivors in this audience. I mean that’s how rampant cancer is. That’s what we’re dealing with. How are we going to stop this, what are we going do about
this as a human race? So I kind of want to throw out
some statistics to you, that are kind of scary for me,
kind of frightening. Men, one in two, half the men
here will develop cancer; one in four will die of cancer. Ladies, one in three will develop; one in five will die of cancer. I mean that really frightens me. We’ve done a lot, but clearly
there is a lot more that we can do. So I am cancer biologist,
I like to study little cancer cells. They are small, you can’t see them. They are a fraction of a millimeter.
We use microscopes to see them. I try to figure out how they behave,
how they function these cancer cells. Today I really wanted to talk
to you about hope. Where does hope live
for this dreadful disease? What are we going to do about this? I’d like to talk to you a little bit about what my laboratory
is contributing to this. And I’d like to talk to you about how us, as an international cancer research
community are handling this. We have been very interested in
understanding the biology behind cancer. We have been very fascinated
by this for a while. And I want to kind
of set a context for you, I want to set a stage for you to understand how
we have been treating cancer, and how we thought about cancer
for a really long time. I could use a little of a personal story. So I am going to work one day,
I am leaving the front door. I am running out, trying
to catch a meeting or whatever. I close the door, wave goodbye
to my kids through the window, and hustle into the car,
and I got to start the car up, right? And turn the key,
and the car doesn’t start. I look up, and there is now smoke
coming out of the hood of my car. Look up again, my kids
that were once waving are now laughing at me, because what could be funnier than
dad’s car with smoke coming out of it? I think about, I got to do something here,
I got to do something about it. What am I going to do,
and I want to go lift up the hood. About ten minutes later,
I find the hood release. I go to the front,
I know nothing about cars, so I lift it up, and indeed,
there is smoke coming out of the car. But I think, I am not a mechanic, but I think that smoke is probably
not the cause of the problem. There is probably
something wrong behind it. Maybe the engine is broken, maybe the carburetor fell off, or the steering wheel
is turned the wrong way, I don’t know. But I can guarantee you
that it’s not the smoke, there is something else. The smoke is here,
but there is an underlying cause. That’s really an analogy for
how we’ve understood cancers for a while. We’ve understood the symptoms
for instance, of cancer. What’s going on at the surface? But we haven’t understood really
the underlying cause, I mean at the molecular level, what is driving the cancer
at the molecular level? We’ve known the symptoms, but what’s happening
at the molecular level? So what are the symptoms
I am talking about? I am going to show you some videos. So my laboratory makes
videos of cancer cells, and we look at how they function,
these are sort of one-of-the-kind, and what you have in front of you
is a video of breast cancer cells. These are 20 breast cancer cells,
watch what happens over three days. Look how the grow. They proliferate. I mean this is scary, right? That’s sort of
the same feeling that I have. Look at them go, they proliferate quickly. This is a symptom we will say of cancer, proliferation or growth. So, what’s fascinating about this is that people that have cancer don’t actually die from the growth,
it’s actually not that. We actually look at
the movement of cancer. This is another symptom,
most people die from the spread. Watch these lung cancer cells,
they are on the bottom-left and top-right, and there is gap in between. Watch how they move. This is over night
underneath a microscope. This is known as metastasis,
this is known as the spread of cancer. When you hear malignancy,
this is what we are talking about. These are the symptoms, we have growth,
and we have spread or movement. But again, what is
the underlying cause of this? What is happening at the molecular level that is causing this to happen? I want to start
with a little bit of history, I think this is really helpful. These are your chromosomes,
we have 46 of them, 23 pairs. On the chromosomes is our DNA code,
3 billion letters, 3 billion letter code. Well, back in the 1990s,
the United States government said: “I want to sequence the entire
DNA code, all 3 billion letters.” And this entire code
is known as the genome, so the project was called
the Human Genome Project. This got a lot of fanfare in media press. It took about two decades to do this, two decades, and it cost
about 3 billion dollars. So about a dollar a letter
in the code, basically. it took quite a while. And we’ve learned a lot of biology
for sure, we learned a lot about it. Fast forward to today, right now,
the technology that we have right now, instead of costing 3 billion dollars,
it cost a few thousand dollars. And instead of taking a couple of decades,
now it takes a couple of weeks. This is a major jump in technology. This is great, we can do this
quicker and faster, it’s only going to get better. We are going to do it
for under 1,000 dollars, and it’s going to take a few days. Perhaps, we may not even do
one human genome, we could do many at the same time. This is great,
we have this great technology. But what about cancer,
what does this mean for cancer? This is the important point. If we could sequence normal cells,
we can sequence cancer cells. It’s obvious, it’s logical. So Imagine this scenario,
every patient who comes into clinic could have their specific
cancer sequenced. And this is really important, because by understanding
the sequence of the cancer, we could then uncover
the molecular changes that occur in their specific cancer. These changes are known as mutations. So we can uncover the molecular
mutations for everybody’s cancer. This has serious therapeutic implications, which I am going to get to. But there are also challenges,
so we paint a very nice picture, but like everything else,
there are challenges. There are challenges that range from
how we are going to store this big data – it’s a popular topic –
to privacy, to biology. And that’s one of those things we work on, is that we are trying to contribute
to this as cancer biologists, to contribute to
this international effort. So what are we doing? Well, this here is a real lung cancer, this is what happens
when someone gets a biopsy, and it goes to a pathologist,
this is what it looks like. If you look at it, it’s not all the same. There are cancer cells in there,
there are those patterns that form. there are normal cells around it, the cancer is in the middle
on that pattern. If we are going to sequence
the entire tumor, the entire cancer, what about the small cancer cells,
the really rare cancer cells that we know are extremely important? They are just going to get lost
in the greater population. How do I go in and say,
I want this cancer cell? These guys are tiny
like a fraction of a millimeter. How do I pick what I want? How do I know
which is the bad cancer cell? How do I know which is the ringleader? That’s what we are trying to do here. This is a model that we create, these are cancer cells, it’s a big ball of cancer cells
with all the cells coming out of it, and you could see they form
these finger-like patterns. Let me frame one more time. Look how they spread out:
there are some cells come out first – these we call leader cells,
or pioneer cells – there are some cells that come out
behind – we call them follower cells – and there are some cells
that never come out. We know those leader cells
at the front are really important. They may in fact drive
the spread in the metastasis. So it’s logical that we need
to know what changes occur, we need to know what changes occur
to target them, to treat them. I will show you how smart this guys are. Watch, here comes out
a single leader cell, and watch what it does, it comes out, and watch;
it makes a U-turn to go get its followers. it makes a U-turn,
it communicates with other cells. Let me frame one more time. It comes out, and it’ll make a U-turn. It wants to have followers, but what makes this cell special,
what makes it important, and how do I pick these cells
and pull them out? This is kind of fascinating for us. So this is a cool technology,
this is something we just developed. We did it in the past year. It combines existing technologies
in a novel way. This is a palette of cancer cells. It’s a green palette; they have a special protein
that comes from a jellyfish that someone won the Nobel Prize
for about five or seven years ago. All the cells here,
there are a couple hundred of cells, they are green
because of the special protein, but it’s a rarely unique green. If we shine laser light on it,
it could turn red. So we could precisely define
an area, the size of a cell – even smaller if we want it to – and turn that specific cell red. What we have created
it is an optical highlighter, just like you would highlight a book, and say I want this word,
I want this letter. We say I want this cell,
these guys are small. Let me just show you a sort of… maybe it’s a little bit of gimmick,
but I’ll show it to you. So you could see, we could turn
those specific cells red. And these guys are
like fractions of a millimeter. And we could pick whatever cells we want. Look at how precise it is, none
of the other cells around it turn red. Look at that precision,
and you can go back and see it. It’s extremely precise. So what do we do with this technology
besides making silly TEDx logos? This is our cell zapping microscope. You could see the screen on the right,
we could choose what cells we want, and we zap the cells,
and they turn red like I just showed you. Then we send it through
another existing technology, and I kind of have
a little animation here about it. Look all the green cells go through,
but now we zap the red cell. So there is our red cell,
and they are very rare, 1 in 10,000 maybe. It gives it a charge, and that single red cell
could end up by itself in a well. It’s like a filter. We could sort out
those red cells by themselves. We could even drop a single red cell
into a well by using this technology. It’s that sensitive, it’s quite cool. That’s how we actually pull out
the cells that we want. What does this look like?
I spoke about those leader cells. What you have there
is a leader cell in green, and there is a white outline
around the front of the cell; and on the right side you have the red. When we convert it to red,
watch how it goes up, the red goes up. Now it’s just the red go up, but the green color goes down
at the same time. So we can pick whatever cell that we want – in a live cell environment, these cells are alive at the time,
and choose what we want – and then we sequence it. Then we are able to determine
the precise DNA code of that cancer cell. What we hope,
and that’s where we are right now, what we hope is that this will reveal
an entirely new signature, a new DNA signature that we could use to identify these cells
and kill these cells. And that’s our goal. What does all this mean?
What’s the bigger picture here? 1.6 million people will be diagnosed
with cancer this year. That’s what we are dealing with. I think all of this technology
that I’ve been talking about, that we’ve been doing, and other people, has two major implications. First off, it’s going to change
the way we classify cancer. Previously, we said lung cancer,
breast cancer, prostate cancer. We thought about where it came from. But instead, we got it classified
on the molecular level. What has changed,
and this is happening right now. We are thinking about
cancers entirely differently. We are reclassifying cancer and say, “It’s not just lung cancer, you have lung caner
with these specific mutations.” And that’s really important for treatment. And the second point is treatment,
why is it so important for treatment? We have our blue people,
and we have our red people. They are all diagnosed with lung cancer. Previously, we said,
“We treat you all the same.” All six people here are treated the same. But that shouldn’t be the case. Because when we sequence, we know that their cancers
are not the same. All cancers are not created alike. They are actually different diseases. Now, we know that the red people
have changes in genes A and B. And the blue people have
changes in genes C and D. So we know
that they are different diseases. So for people who have
changes in genes A and B, we treat it with treatment 1, and we already have treatment 1, and it’s great, it works,
and it’s very, very effective. With people with
mutations in genes C and D, we give them treatment 2, and maybe we don’t have
treatment 2 yet, but we are working on it. That’s what’s going to take time. This whole concept is called
personalized cancer medicine, because we are
personalizing treatment. It also goes by the name
personalized oncology as well but this here is the biggest change
we are going to make. It’s not some fantastic new treatment, instead, we are treating people
more logically than we ever had before. In fact, we may need to bring back
or resurrect fail drugs, because maybe we weren’t giving them
to the right people. Maybe we need to give them back,
and give them to the right people. I want to end on a more personal note. This here is Jonathan Hex,
he is 28 years old, diagnosed with stage IV lung cancer. Lung cancer has
a 15% survival rate after 5 years, only 15% people are alive. There is no stage V. He never smoked a day in his life. Because of personalized cancer medicine,
he has his tumor sequenced. It was found out he had a change,
and we had a treatment for it. We have a treatment for it. He is now alive today
because of personalized cancer medicine. He got married, even made a short film
about it called Nirvana. This is where the promise is, this is the next great revolution
in cancer treatment. Thank you for your time. (Applause)

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