The Role of DNA Repair and Damage in Cancer

July 12, 2021

Information

July 11, 2021

Yale Cancer Center

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00:00Funding for Yale Cancer Answers
00:02is provided by Smilow Cancer
00:04Hospital and AstraZeneca.
00:08Welcome to Yale Cancer Answers with
00:10your host doctor Anees Chagpar.
00:12Yale Cancer Answers features the
00:14latest information on cancer care by
00:16welcoming oncologists and specialists
00:18who are on the forefront of the
00:20battle to fight cancer. This week,
00:22it's a conversation about DNA
00:24repair with Doctor Megan King.
00:26Doctor King is an associate professor
00:28of cell biology and of molecular,
00:31cellular, and developmental biology
00:32at the Yale School of Medicine,
00:34where Doctor Chagpar is a
00:37professor of surgical oncology.
00:39Megan, maybe we can start off with you
00:42telling us a little bit about yourself
00:45and about your research and how you got
00:47involved in this research project to
00:50begin with.
00:50Yeah, so it's very interesting thinking
00:52back to what drew me towards science.
00:55I'm from a family of engineers,
00:57actually including both of my parents,
00:59but I always gravitated towards science,
01:02and in particular as a high school student,
01:04I took anatomy and Physiology,
01:06and it was actually the
01:08section of my textbook
01:09on cancer that really provided for me,
01:12I think the first kind of window into
01:14how a scientist could have a positive
01:17impact on human health in a way that was
01:20different from becoming a medical doctor,
01:22which I think all of us are a
01:25little bit more familiar with,
01:27certainly as children.
01:28And so I've been reflecting on
01:30that recently because it's been a
01:32bit of a circuitous route that's
01:34brought me back to Cancer Research.
01:36I really trended towards very
01:38fundamental kind of basic science.
01:40Questions for my initial training
01:42as an undergraduate and graduate
01:44student and even into my
01:47postdoc period where one typically
01:49is defining the kind of areas of
01:51research that they will pursue,
01:53and in their independent laboratory.
01:55But I discovered a connection between
01:57the cell biology of the nucleus,
02:00which is something that I had
02:02been training with
02:04Gunter Blobel at Rockefeller
02:06University in Genome Integrity,
02:07so that is the mechanisms that
02:10maintain the DNA blueprint
02:12as it should be and that was
02:14really just something that I had
02:16not focused on before
02:18but it really changed the direction of
02:21my research and I became very interested
02:24in how aspects of how a cell works,
02:26are able to contribute to the mechanisms
02:29that maintain that genetic code.
02:31So tell us more about
02:33that. I think some of us can
02:35remember back to junior high biology
02:38where we kind of know what a cell is.
02:41And we know what a nucleus is and
02:44housed within that nucleus is the
02:46DNA which is responsible for that
02:48genetic blueprint as you say.
02:50So tell us more about the connection
02:52that you found between how a cell
02:55functions and genomic integrity.
02:56Yeah, so I was
02:58also fascinated with this
03:00idea of the the nucleus which
03:02is the organelle that houses the DNA,
03:05being kind of the brain.
03:07Having all of the kind of
03:09control and that plan
03:11for the cell, but I think one of the
03:14things that maybe isn't always captured
03:16when we kind of make that diorama during
03:19you know grade school is that actually
03:22it's not just a big ball of yarn,
03:25but actually the DNA has lots of different
03:28regions and these regions are important
03:30for different aspects of that blueprint.
03:33And they're not all created equal.
03:36There are specific regions of the DNA
03:39that are far more prone to damage.
03:42And there are also mechanisms to repair
03:44that damage that may be quite specific,
03:46so if you have a leak
03:49in a pipe you may need a plumber, right?
03:52But if you're siding
03:54has gone downhill,
03:55maybe you need someone who is
03:57more like a Carpenter.
03:59Or for any
04:00new paint you're going
04:02to have a different kind of approach
04:04depending on what the issue is.
04:06And it turns out for cells,
04:08that's similar.
04:09There are actually different
04:10DNA repair mechanisms and you
04:12really need to use the right mechanism
04:14for the right kind of damage,
04:17and it turns out that much of that is
04:19actually dictated by these different
04:21flavors of the regions of DNA and
04:24also physically where those different
04:26regions of the DNA blueprint are
04:29organized inside the nucleus,
04:30because it's a much more
04:33compartmentalized kind of network
04:37than when we just again think of
04:40this string that has all of that
04:43coding material,
04:43so it's not
04:44just where the break occurs in the
04:47DNA or what kind of a break it is,
04:50whether it's a single strand
04:52break or a double strand break,
04:54but where exactly it's
04:56located within the nucleus.
04:58We think about two components.
05:00One exactly as you say physically,
05:03where is that DNA break in the nucleus?
05:06And then there's also the
05:07other attributes of the DNA.
05:09So DNA doesn't live on its own.
05:13It's actually wrapped up and packaged
05:15around proteins that are called
05:17histones and this packaging is
05:19really important for whether a
05:22particular gene may be expressed or not.
05:24It turns out that a DNA break
05:27in a region of the genome
05:29that is coding for a protein,
05:31so it's going to be transcribed
05:33into the messenger RNA and then
05:36translated into a protein.
05:37Those regions of the genome are
05:39a bit different than regions of
05:41the genome that may be silent,
05:43and so that also just leads to both some
05:46challenges for DNA repair mechanisms
05:48and also some activities that
05:51may actually make it more prone to
05:53the accumulation of DNA damage.
05:55And so we think of both
05:57where the break is
05:59physically,
06:00and also where it is in context
06:02of what else is happening in
06:04that region of the DNA.
06:06So we know that DNA can incur various
06:09forms of damage that can be in coding
06:12regions or in non coding regions.
06:15How does that then evolve into
06:17your research with cancer?
06:19So initially as I mentioned our
06:21interest was the idea that these
06:24different locations in the nucleus
06:26might be important for making sure that
06:29those breaks are repaired by the right
06:31process and in order to study that we
06:35really need to be able to watch DNA
06:38repair in a cell that's living while
06:40it's happening and that as it turns out
06:42is actually quite a difficult problem,
06:45and so over the past ten years or so,
06:48one of the things that my group has
06:50invested in, is building so called
06:52assays where we can actually watch
06:55a single DNA break,
06:56which we actually control.
06:58So we induce the break to occur in
07:00exactly the place where we want it to,
07:03and then we actually follow the
07:05repair of that break in real time and
07:08once we built this system,
07:10we became very interested in how we might
07:13leverage it to answer some important
07:15questions that were really arising
07:17in the field of cancer treatments.
07:19And really,
07:20I was driven towards those questions
07:22through my interactions with my
07:24fantastic colleagues here
07:26at the School of Medicine and at
07:29Yale Cancer Center who really brought
07:33a way of connecting the kind of questions
07:36that I had become interested in,
07:38again as a postdoc and kind of just
07:41looking through the microscope
07:42to where we had a real need to
07:45understand specific questions in
07:46the field of DNA repair,
07:49and particularly those that were
07:50relevant to the kind of therapies
07:53that might be used in the context
07:55where patients have
07:56defects in DNA repair within their tumors.
07:59So first question,
08:00how exactly do you watch DNA being
08:03repaired in real time?
08:05I'm kind of blown away by that concept.
08:09I remember back in junior high
08:11biology looking down a microscope at
08:13a cell and looking at the nucleus.
08:16And sometimes you could even see DNA
08:19separating into mitotic figures and so on.
08:22But to actually see DNA being repaired?
08:24I mean presumably that occurs at a base pair
08:28level and that's just fascinating to me.
08:31So how exactly do you do that
08:33and what kind of magnification
08:35would you need even to see that?
08:38Yeah, that's a great question and honestly,
08:40this is why I'm a cell biologist at the end
08:43of the day because we love to just look.
08:46If we have a way we can look at
08:48something happening in real time that
08:50is always the best thing in the world.
08:53However, as you say,
08:54it's not easy and so our work is built
08:56on really critical discoveries that
08:58have driven cell biology, in particular,
09:00and I'll just tell you about two
09:02of those that are critical for
09:04the assays that we've built.
09:05The first is the advent of
09:07these fluorescent proteins.
09:08Green fluorescent proteins
09:09and red fluorescent proteins.
09:11Now we have an entire rainbow
09:13of these fluorescent proteins,
09:14and so these are proteins that
09:16fold up and they're able to make
09:19what's called a chromophore
09:20and we can actually follow that
09:22specific molecule in a microscope.
09:24And what we do is we basically stitch
09:27that fluorescent protein onto a
09:29protein that we're interested in,
09:30and now we can follow our favorite
09:33protein of interest in a live
09:35cell on a fluorescence microscope
09:36that can specifically detect
09:38that fluorescent protein,
09:39and so that's one technology
09:41that's absolutely critical.
09:43The other,
09:43and I think this really speaks to
09:46the importance of kind of basic
09:48science discoveries and what
09:50really has impacts on human
09:52health these days is that we use
09:55tricks to insert a region that's
09:57actually taken from a bacteria,
09:59so it's not native to the cells
10:01that we are modifying,
10:03and we essentially take that little sequence,
10:05and we put it into the place in the genome
10:09we're interested in and then we
10:11have a protein that can bind to
10:13that very specific DNA sequence,
10:15and so we can monitor any kind of
10:18region of the genome that we want
10:20just by doing a little bit of editing
10:23to that genome and putting these
10:25in bacterial gene sequences
10:27into our eukaryotic cell,
10:28because that's what we want to be studying.
10:31In terms of the magnification,
10:33you're absolutely right.
10:34We are able to do a pretty good
10:37job following these events
10:39even with a magnification,
10:41usually between 100 and 1000 fold over
10:44what you could see with the naked eye.
10:47Wow, so essentially you can clip the
10:49DNA where you want to make a break.
10:52Insert a bacterial strand of genetic
10:55material, flag it with a particular
10:57flag so you know where the break is and
11:00then have these chromophores which can
11:03light up when they approach that break.
11:09That's right, so another critical aspect is
11:11we have to know a lot about DNA repair,
11:13and fortunately,
11:15DNA repair has been a really rich
11:17area of research for many decades,
11:19and so building again on the knowledge
11:21of many others we know pretty well
11:23about the kind of timing and the events
11:25that are taking place and repair.
11:27So protein X shows up,
11:29and it always shows up before protein Y.
11:32And as you said,
11:33we want to know what's happening
11:35at the base pair level,
11:37like the smallest unit of DNA.
11:39We can't really see something
11:41that small in this assay,
11:42so we're using proxies of factors
11:44that we know will show up at different
11:47points and that allows us to
11:49essentially monitor distinct events,
11:51because if we build up our
11:54library of these different flags that
11:56indicate different times and repair
11:58them more able to monitor those events,
12:01and we're also able to
12:03monitor them in single,
12:05individual cells,
12:06and it's turned out that that's
12:08really important.
12:09Because if we look at a million
12:12cells doing something they all kind
12:13of do it on a little bit different
12:16time over a little bit different time,
12:18then the cell next
12:20door and so by actually watching
12:22these events in single cells,
12:24that really gives us a resolution
12:26that's really important for
12:27being able to make very
12:29mechanistic conclusions from the data.
12:31So we understand that you've got
12:33DNA that can get injured and it can
12:36get injured in a variety of ways
12:39at a variety of places,
12:41each of which requires a
12:43specific mechanism to repair it.
12:45And we now understand that you've
12:47built this model to kind of see
12:49how DNA repairs itself overtime,
12:51so tell us more about how this gets
12:53into cancer and into therapeutics
12:56And we'll have to do that as soon as
12:59we take a break for a medical minute.
13:02So please stay tuned to learn more about
13:05DNA repair and cancer with my guest
13:08Doctor Megan King.
13:09Funding for Yale Cancer Answers
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13:18Learn more at astrazeneca-us.com.
13:21Breast cancer is one of the most common
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13:27approximately 3500 women will be
13:29diagnosed with breast cancer this year,
13:31but there is hope,
13:32thanks to earlier detection,
13:34noninvasive treatments and the development
13:36of novel therapies to fight breast cancer.
13:38Women should schedule a baseline
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13:43earlier if they have risk factors
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13:52Clinical trials are currently
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13:56Comprehensive cancer centers such
13:58as Yale Cancer Center and Smilow
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14:03new treatments available to patients.
14:05Digital breast tomosynthesis, or 3D
14:07mammography is also transforming breast
14:10cancer screening by significantly
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14:13while picking up more cancers.
14:15More information is available at
14:18yalecancercenter.org. You're listening
14:20to Connecticut Public Radio.
14:22Welcome
14:22back to Yale Cancer Answers.
14:24This is doctor Anees Chagpar and I'm
14:27joined tonight by my guest doctor Megan King.
14:31We're talking about DNA repair and cancer,
14:33and right before the break we had
14:36gotten to the point in the story
14:39where we were talking about the fact
14:41that DNA gets injured and it can
14:44get damaged in a variety of places.
14:47And each of these breaks may be
14:49specific and may require a specific
14:52mechanism to repair it and we also
14:55talked about the fact that Doctor King's
14:58laboratory had figured out a way to
15:01actually watch how DNA gets repaired.
15:04right under a microscope,
15:06which was just fascinating.
15:08But now Megan,
15:09maybe you can help us to understand
15:11how this really evolves into
15:13understanding a little bit more
15:14about cancer and therapeutics.
15:16We built the capability now of
15:19monitoring DNA repair and these single cells.
15:22And now we get to the point
15:24in a basic scientist life where you
15:27think about, I've built this assay,
15:30it took us many years to do it.
15:33What do we want to study?
15:35And it's about this time that I had
15:38been interacting increasingly
15:40with members of Yale Cancer
15:42Center and hearing about their
15:44work in the clinic and their work
15:47that is more translational.
15:49So that's when we kind of apply basic
15:51science and fundamental principles,
15:53directly to new treatments.
15:56And through these interactions we became
15:58very interested in how we might use this
16:02assay to answer a question that has arisen
16:05that was clearly critical to the treatment
16:07of breast and ovarian cancer that is
16:09tied to this familial cancer susceptibility
16:12genes BRCA one and 2.
16:14I allways have a soft spot in my heart
16:16for BRCA 1 because it
16:19was discovered by Mary Claire King.
16:20No relation but we have the same
16:23initials and last name and in fact
16:25over the years I've gotten emails
16:27intended for Mary Claire King.
16:29So we've struck up already a kind
16:31of back and forth just because
16:33of people getting us mixed up.
16:37And so BRCA one really had
16:40become a success story of an approach
16:43to therapy called synthetic lethality.
16:46And so the idea is that
16:48BRCA one is very important,
16:51particularly in a type of DNA repair
16:54called homologous or combination
16:55and in individuals who have a
16:58loss of function and BRCA one,
17:01this leads to an increased susceptibility
17:03to breast and ovarian cancer in women.
17:07And so you are probably quite familiar
17:09with this because it's become very well known.
17:13And it's also well known
17:15even on the scientific front
17:18because of the advent of a therapy
17:20which is called PARP inhibitor
17:22therapies that specifically kill
17:24tumor cells that are defective in the
17:27functions of BRCA one or two,
17:29and actually more broadly in DNA
17:32repair through this mechanism
17:33called homologous recombination.
17:35And so this is fantastic.
17:37What does that mean for a patient?
17:39It means that all of their normal
17:42tissues can tolerate these drugs.
17:44They really only attack the cells
17:46that don't have functional DNA repair.
17:48So DNA repair is this kind of
17:50double edged sword, on the one hand,
17:53a defect in DNA repair can lead
17:55an individual to be vulnerable
17:57to developing a cancer.
17:58But if the cancer is defective
18:01in DNA repair,
18:02it also opens up a window
18:04for therapies and PARP
18:05Inhibitors were something that
18:07could kind of fit into that window,
18:09so this was really a very exciting
18:12time and continues to be a really new
18:14approach to treating cancers that are
18:16tied to homologous or combination
18:18defects which we now know include a
18:21number of contexts that do not involve
18:24just BRCA 1 and 2.
18:26However,
18:27we also knew quite early on
18:29that these patients
18:30would often have acquired
18:31resistance to the PARP inhibitiors.
18:33They would initially respond very well,
18:35but the response would not
18:37be as durable as they and their
18:40physicians would like it to be,
18:42and investigators had gone in to
18:44try to ask how is it that these
18:47tumors are evolving, essentially,
18:48to become resistant to PARP inhibitors,
18:50and particularly in the case of BRCA 1
18:53they found that there
18:55seemed to be secondary loss
18:57of other repair factors that were
18:59involved and we became excited
19:02about the potential of our assay
19:04to maybe provide some insight
19:07into how is it that these tumors
19:09are getting around this therapy,
19:12and even more importantly,
19:13might there be ways that we could
19:16actually target these cells again?
19:19So kind of re-sensitize them
19:21to PARP inhibitors,
19:23and so we modeled these mutations,
19:29so that cells no longer express a number
19:32of other factors called 53BP1
19:34on a complex called shieldin.
19:37And somehow this allows cells that
19:40don't have functional BRCA one
19:42to still survive in the presence
19:44of PARP inhibitors,
19:46and so we investigated those using
19:48this assay and we discovered that the
19:51loss of these factors that drove
19:54this PARP inhibitor to no longer work were
19:57affecting DNA repair in a very
19:59specific way by unleashing
20:01a DNA repair factor that really
20:03shouldn't be functioning and this is
20:05a protein called the bloom's helicase
20:07and it was able to kind of step in for
20:10BRCA one when these other factors
20:12are silenced and take over and so
20:15in a sense that seems like a bad thing.
20:17Some other protein can come in and
20:19and take the place of BRCA one,
20:22but it turns out one of the things we
20:24learned in our experiments was that
20:26there was kind of a new liability.
20:29That this activation of this
20:31bloom's helicase brought along,
20:33and it's actually now this
20:36angle that we're targeting,
20:37with the idea that there will be
20:41new combination therapies that will
20:43re sensitize these tumors to PARP
20:45inhibitors in combination with either
20:48inhibitors of the bloom helicase itself,
20:51but also some other additional
20:54treatments that have already been being
20:57pushed forward.
21:00Things like the DNA damage checkpoint,
21:02which is something that acts
21:04downstream of unresolved DNA damage,
21:05so we're pretty excited that these
21:08kind of very fundamental insights
21:10from this assay that I've described
21:12are really leading us to consider
21:14new combinations of drugs that
21:16may allow for
21:18not necessarily to make the PARP inhibitor
21:20but be a good therapy on its own for longer,
21:24but how we might use combinations
21:26that will allow for a very
21:28durable response for these patients.
21:30Let me make sure that we've got
21:33that straight for all of our listeners.
21:35So normally everybody has functional
21:38BRCA but when you have a mutation in
21:41that it no longer becomes effective
21:44and the function of that BRCA gene is
21:47really to repair DNA because DNA we
21:50have in all of our cells and sometimes
21:53it can just get damaged and BRCA
21:57actually forms is a very important gene
22:00that can help us to repair that DNA,
22:03but when that's defective we get cancers.
22:06But these PARP inhibitors
22:09are very effective against tumors
22:11that have DNA damage that is not
22:15being repaired by BRCA.
22:16But then you've got this bloom helicase
22:20which can step in for BRCA.
22:24It's almost like a fail
22:27safe kind of belt and suspenders
22:31where if one
22:34repair mechanism doesn't work,
22:36then another repair mechanism can work,
22:38but in cancer cells you really
22:40don't want it to work.
22:42So what you're now doing is trying
22:45to find inhibitors to that secondary
22:47repair mechanism to ensure that the PARP
22:50inhibitors can kill off those cancer cells.
22:54Yes, that's exactly right,
22:55and it had been known for a while that
22:58there might be these two kind of parallel
23:01mechanisms to carry out a specific
23:04step in homologous recombination and
23:06indeed, it was known already that
23:08these two mechanisms existed,
23:09but actually we didn't know very much
23:12about how a cell could decide to use one
23:15mechanism that would be this kind of BRCA
23:17one mechanism which works with
23:21this blooms' helicase pathway,
23:22which as you said is kind
23:24of a backup mechanism.
23:25One of the things we've discovered is that
23:28we think that the bloom's helicase mechanism,
23:30although it's a backup,
23:31it's really not supposed to
23:33be working in normal cells,
23:35and that's why there are a number of factors
23:38that keep it off and that
23:40includes these proteins,
23:41the loss of which can drive
23:43PARP inhibitor resistance.
23:44So we think that actually there's
23:46kind of a gain.
23:47We would call it a gain of function
23:49of the bloom's helicase that underlies
23:52the PARP inhibitor resistance.
23:54Why might cells not want to be using
23:56this bloom's helicase all the time?
23:58We think that it's because actually it's
24:01not a very well controlled enzyme,
24:03so its activity in the repair process
24:06kind of goes wild a bit.
24:09And even though this allows the cells
24:11to get around the PARP inhibitor,
24:13it actually may make them susceptible to
24:17additional targets
24:18that are being developed,
24:19and so we think
24:21just like a DNA repair defect
24:23opens up a therapeutic window,
24:25we think this kind of rewiring from
24:28BRCA one to the bloom's helicase may
24:30also open up new ways that we could
24:33go about treating these tumors.
24:35So then the next question is,
24:37is there a way for us to
24:40figure out either upfront before
24:42we give any therapy whether a
24:44particular patient is going to have
24:47this bloom's helicase turned on or not,
24:49so that upfront we can decide whether
24:51we should just give up our PARP inhibitor,
24:54or whether we need to give dual
24:56therapy or in a productive manner
24:58where we can say, well,
25:01if somebody hasn't responded to the
25:03PARP inhibitor as we would anticipate,
25:05is there a way for us to figure out
25:08if this is the mechanism by which
25:11the cell is getting around that
25:13PARP inhibitor and developing resistance
25:15so that we can add in another drug.
25:17Do we have those kinds of diagnostics?
25:21You're absolutely right,
25:22this is exactly what we would like to have,
25:25but we don't have it yet,
25:27so we would like to be able to take a
25:32tumor sample and ask the question,
25:34what is happening in this tumor?
25:36Is this patient likely to
25:38respond to the PARP inhibitor?
25:40We know that if they have
25:41a defect in DNA repair,
25:43they're likely to respond.
25:45We know, as I told you, this bloom's
25:47helicase tends to go kind of overboard,
25:49and we think that we can design
25:52what we would call a
25:53biomarker of that activity,
25:55because it generates far too much of
25:57this single stranded DNA generating
25:59single strand of DNA is a critical
26:01part of homologous or combination,
26:03but again,
26:04bloom's helicase seems to do too much of this,
26:07and we think that we might be
26:09able to use proteins that bind
26:11to that single stranded DNA,
26:13kind of quantitatively,
26:14and that may be an indication
26:16that this is the mechanism by which
26:19these cells elevated PARP inhibitors.
26:21Another major mechanism
26:22of PARP inhibitor resistance
26:23are so called reversion mutations.
26:25This is where there's actually a
26:27second mutation in the BRCA gene,
26:29which essentially can reconstitute
26:30its normal function.
26:31In this case,
26:32the tumor no longer has
26:34a DNA repair defect,
26:35and so we'd really like to
26:37be able to tell is there a
26:39reconstitution of normal repair.
26:41But maybe that repair still has
26:43some defects that we can target,
26:45or is repair kind of totally normal,
26:47in which case we know we're going
26:49to have to think about another
26:51type of therapy to treat that patient.
26:53So these are in development and
26:55this is something we're really
26:57interested in,
26:59particularly again with our
27:00colleagues here and at Yale Cancer Center.
27:02To continue to push forward by
27:04partnering with those clinicians who
27:06are running clinical trials in this space.
27:09In patients with BRCA or NOTE Confidence: 0.98452777
27:11other homologous recombination
27:12defects who have been enrolled
27:13on PARP inhibitors and looking at
27:15those resistance mechanisms.
27:17And if we can develop these
27:19types of biomarkers.
27:21I mean it's so fascinating
27:23thinking about the fact that
27:26when we started this conversation,
27:28we started by saying that you know DNA
27:30can be damaged in different ways and each
27:33requires a specific repair mechanism.
27:35But now thinking about how you're
27:38actually taking your science
27:40and in a way kind of again,
27:42moving towards personalized medicine,
27:43figuring out, well,
27:44if somebody develops resistance,
27:47how exactly is that resistance
27:49mechanism functioning?
27:49And how can we get around it?
27:54Absolutely, and I want to highlight
27:56we can do this really efficiently
27:58in cells in a laboratory that's
28:00never going to tell us about what
28:02is happening in individual patients.
28:05So really, this discovery requires the
28:07commitment of patients who've been
28:09enrolled on these clinical trials.
28:11That's not an easy thing to
28:13ask of patients in this case.
28:15For example, they've signed up for
28:17serial biopsies of their tumor,
28:19but that is absolutely essential
28:21for us to continue to discover
28:24the mechanisms that are at play and for
28:26us to come up with better treatments.
28:29Doctor Megan King is an associate
28:31professor of cell biology and of molecular,
28:33cellular, and developmental biology
28:35at the Yale School of Medicine.
28:37If you have questions,
28:39the address is cancer answers at
28:41yale.edu and past editions of the
28:43program are available in audio and
28:45written form at yalecancercenter.org.
28:47We hope you'll join us next week to
28:49learn more about the fight against
28:52cancer here on Connecticut Public Radio.
28:54Funding for Yale Cancer
28:56Answers is provided by Smilow
28:58Cancer Hospital and AstraZeneca.