Genomic Causes of Cancer Progression and Therapeutic VulnerabilityDecember 13, 2021
December 12, 2021
Yale Cancer Center
To CiteDCA Citation Guide
- 00:00Funding for Yale Cancer Answers
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- 00:04Hospital and Astra Zeneca.
- 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
- 00:17who are on the forefront of the
- 00:20battle to fight cancer. This week,
- 00:22it's a conversation about genomic causes
- 00:24of cancer progression and therapeutic
- 00:26vulnerabilities with Doctor Jason Sheltzer.
- 00:27Dr Sheltzer is an
- 00:29assistant professor of surgery and
- 00:31oncology at the Yale School of
- 00:33Medicine where Doctor Chagpar is
- 00:35a professor of surgical oncology.
- 00:38Jason, maybe we can start off by
- 00:39you telling us a little bit about
- 00:41yourself and what exactly you do.
- 00:43Sure, so despite my departmental affiliation
- 00:45I am neither a surgeon nor an oncologist.
- 00:49I am a basic science researcher.
- 00:52I have a PhD in molecular biology
- 00:55and my lab studies the genetic basis
- 00:58of cancer development and cancer
- 01:01therapeutic responses from a basic
- 01:04or a non clinical perspective.
- 01:08That sounds pretty interesting,
- 01:09but it also sounds pretty broad.
- 01:11We talk a lot on
- 01:15this show about the genomic and
- 01:17genetic underpinnings of cancer,
- 01:19so tell us a little bit
- 01:20more about your research,
- 01:22sure, so overall, I think that it is a
- 01:26really remarkable time in cancer biology.
- 01:29There are a ton of exciting
- 01:32advances happening at Yale and at
- 01:35institutions around the world,
- 01:36and there are just rapid advances
- 01:38in so many areas that are really
- 01:41directly contributing to patient care.
- 01:43In my own lab, were interested in using
- 01:46different genetic techniques to model
- 01:49certain alterations in chromosomes
- 01:51that you commonly see in cancer.
- 01:54So in cancer cells most normal cells
- 01:57in your body have 46 chromosomes,
- 02:0023 pairs of chromosomes,
- 02:02but for some reason cancer cells almost
- 02:04all have the wrong number of chromosomes.
- 02:06Cancer cells have 47 chromosomes or
- 02:0948 chromosomes, or 140 chromosomes,
- 02:11and no one really.
- 02:13Understands how that happens or why?
- 02:16Why that contributes to tumor
- 02:18growth and my lab tries to generate
- 02:21techniques to model these chromosome
- 02:23changes so we can understand how
- 02:25they contribute to cancer.
- 02:28OK, so I guess there's a few
- 02:31questions to unpack there.
- 02:33The first is why do cancer cells have
- 02:36a different number of chromosomes
- 02:39and what impact does that have
- 02:41on cancer development, right?
- 02:44So there are two schools of thought there,
- 02:46so on one hand, some people think that
- 02:49this is just like an accident of cancer.
- 02:52Cancer cells do a lot of things wrong.
- 02:55They're they're very genomically unstable.
- 02:57They have all sorts of errors that occur
- 03:00during the cell cycle, and so some
- 03:03scientists think that the aneuploidy,
- 03:06which is another word for the chromosome copy
- 03:09number alterations that we see in cancer.
- 03:12Some scientists think that this
- 03:14aneuploidy is just kind of a byproduct
- 03:16of things going wrong in cancer,
- 03:18and that it doesn't really
- 03:20have a functional importance.
- 03:21On the other hand,
- 03:23other scientists believe that these
- 03:26chromosome copy number alterations are
- 03:28directly influencing the development
- 03:31and the progression of cancer and the
- 03:34idea there is that these chromosome
- 03:37copy number changes are influencing
- 03:39the number of copies of a gene you
- 03:43have in a cell instead of having
- 03:45two copies of a gene like you would
- 03:48in most normal cells in your body,
- 03:50you may have three copies.
- 03:52Or four copies or 25 copies of a gene.
- 03:55And if that gene has tumor
- 03:58promoting properties,
- 03:59then having 25 copies of that gene
- 04:02might directly contribute to cancer.
- 04:05So so a few questions.
- 04:07The first question is there
- 04:10are some congenital anomalies,
- 04:13some congenital conditions.
- 04:14So I'm thinking about things
- 04:17like Klinefelter syndrome or
- 04:19Down syndrome where people
- 04:22may have an altered number of
- 04:26copies of certain chromosomes.
- 04:28Does that mean that those people
- 04:30by definition are at increased
- 04:31risk of developing cancer,
- 04:34yeah? It's it's a really
- 04:37interesting and important question.
- 04:39Down syndrome is a developmental
- 04:42disability caused by having
- 04:44three copies of chromosome 21.
- 04:47It's the most common genetic cause
- 04:50of developmental disability in EU.
- 04:53S individuals with Down syndrome
- 04:56have a significantly greater risk
- 04:59of developing leukemia and other
- 05:01blood cancers during their lifetime.
- 05:04At the same time, for reasons that
- 05:06I think are very poorly understood,
- 05:09individuals with Down syndrome actually
- 05:11have a significantly decreased risk
- 05:14of developing most solid cancers.
- 05:17Individuals with Down syndrome
- 05:18have lower rates of colon cancer,
- 05:21breast cancer, brain cancer,
- 05:24and I think that that discrepancy
- 05:26is is very poorly understood,
- 05:29and so how do you square that
- 05:32with the concept of the thought?
- 05:34At least the one school of
- 05:36thought of some scientists.
- 05:38As you point out that having a.
- 05:41Discrepant number of copies of a chromosome.
- 05:44So if you've got more copies than
- 05:46you're producing more gene products,
- 05:49more proteins.
- 05:49Cancer cells are more likely to go
- 05:52awry that predisposes to cancer,
- 05:55whereas these people have
- 05:56a lower risk of cancer.
- 05:59How do you square those two phenomena?
- 06:02Yeah, that's a terrific question.
- 06:04So in your cells,
- 06:06not all chromosomes are equivalent.
- 06:09Not all genes are equivalent.
- 06:11There are some genes.
- 06:12That when you have them
- 06:14present in extra copies,
- 06:15they may promote cancer and
- 06:17there are other genes that when
- 06:19you have them in extra copies,
- 06:20they may actually suppress cancer.
- 06:22They prevent the development of
- 06:24cancer and there's a further layer of
- 06:28complication in that different tissues
- 06:30in your body are different as well,
- 06:32and so a gene that has a
- 06:35certain function in blood cells.
- 06:36It may have a different function,
- 06:38or it may have no function
- 06:41whatsoever in mammary gland cells.
- 06:43Or in neurons,
- 06:44or in any other cell type in your body.
- 06:46And so the current commonly accepted
- 06:50explanation for the Down syndrome
- 06:53cancer phenomenon is that there
- 06:55are genes on chromosome 21 which
- 06:58promote the development of cancer
- 07:00in blood cells which promote
- 07:02the development of leukemias,
- 07:04which are what are commonly observed
- 07:06in individuals with Down syndrome.
- 07:08But these genes or other genes
- 07:11on chromosome 21.
- 07:13May actually suppress the development
- 07:15of cancer in other tissues,
- 07:17and it's a really strange phenomenon,
- 07:21and the relationship between the
- 07:22copy number of these genes and the
- 07:25copy number of genes in general
- 07:26and the development of cancer.
- 07:28I think there's a lot more to explore
- 07:30there that science doesn't yet know.
- 07:33And I guess the other question is if
- 07:36I understood you correctly earlier,
- 07:39you were saying that this copy
- 07:41number phenomenon is is quite
- 07:42common in cancer, is that right?
- 07:44Yep, about 90 to 95% of cancers have the
- 07:49wrong number of chromosomes in them.
- 07:51So my next question has to do with this.
- 07:56Is it that there's the wrong
- 07:58number of copies of a particular
- 08:01chromosome in the cancer cell?
- 08:03Or is this a germline phenomenon,
- 08:06so we know that for example in Down
- 08:09syndrome it's a germline phenomenon.
- 08:11You have an extra copy of chromosome
- 08:1421 in all of the cells in your body,
- 08:17whereas it seems to me that you know
- 08:20if we know that most cancers have this.
- 08:23Most cancers are also going to
- 08:26occur in people who do not have any
- 08:29kind of aneuploidy. Is that right?
- 08:31So so it is it more that cancer cells?
- 08:35Acquire extra copies as they move
- 08:39along their cancer Genesis pathway.
- 08:43so I think that we can say that
- 08:46most of the chromosome alterations
- 08:48that occur in cancer are cymatic
- 08:51or they occur during the body over
- 08:54a lifetime and are not germ line.
- 08:56That is, you aren't born with them,
- 08:59but they instead accumulate
- 09:01overtime more broadly.
- 09:04A lot of research has been done
- 09:08indicating how different mutations or
- 09:10single base pair changes can occur over
- 09:13a person's lifetime and contribute
- 09:16to their cancer risk overtime.
- 09:19In addition to these point
- 09:21mutations which contribute to cancer
- 09:23development and occur overtime,
- 09:25there's increasing evidence
- 09:27that overtime your cells will
- 09:29accumulate more aneuploidy or more
- 09:32chromosome copy number errors.
- 09:34As well,
- 09:35so if you look in cells that are
- 09:37isolated from say an 80 year old
- 09:39person and compare them to normal
- 09:41cells that are isolated from say 20
- 09:44year old person in general the 80
- 09:46year old will have significantly more
- 09:49aneuploidy or chromosomal errors in
- 09:52their tissue than the 20 year old,
- 09:55and this may be one of the unexplored
- 09:58or underexplored causes of why
- 10:02cancer incidence increases with age.
- 10:05Because of these somatic chromosomal
- 10:07alterations that are developed overtime
- 10:10and so is it. The concept that if
- 10:13you could somehow reverse that
- 10:15process or stop that process
- 10:18such that people did not acquire
- 10:20aneuploidy as they grew older,
- 10:23that you could actually
- 10:26potentially stop certain cancers.
- 10:29Absolutely, that would be an incredibly
- 10:33exciting cancer prevention strategy.
- 10:35If it was true, there is and we just
- 10:39don't yet know again to contrast
- 10:42the the research on aneuploidy or
- 10:45chromosomal changes with the research
- 10:48on mutations and DNA base pair changes.
- 10:52A lot of research has been done trying
- 10:55to develop strategies to delay the
- 10:57development of point mutations over age.
- 11:00People have talked about antioxidants and
- 11:03vitamin C as some potential strategies.
- 11:06I don't think there's there's good
- 11:07evidence for their strategies,
- 11:08but those are some of the strategies
- 11:11that have been described for the
- 11:13prevention of point mutations for
- 11:15the prevention of chromosome errors.
- 11:17Almost nothing is known,
- 11:19and this is absolutely something that
- 11:21my lab plans to study at Yale to see
- 11:24if we can prevent the development
- 11:26of aneuploidy overtime,
- 11:27and if that would subsequently slow
- 11:30or delay the development of cancer.
- 11:34So tell us more about about that.
- 11:36How do you plan on doing those experiments,
- 11:39and what might we have to look
- 11:41forward to in the future? Yeah,
- 11:44there is a lot that we are planning to do.
- 11:48In general, I think that there are certain
- 11:52proteins that are known to control
- 11:55the process of chromosome segregation.
- 11:58These were proteins that were first
- 12:01discovered in simple single celled organisms.
- 12:04Like budding yeast Saccharomyces service,
- 12:07yeah, the basic process of chromosome
- 12:09segregation was worked out in in these
- 12:12simple organisms and then later research
- 12:15demonstrated that these same genes
- 12:17that function in simple single celled
- 12:19eukaryotic organisms also function
- 12:21in human cells and in cancer cells
- 12:24to control chromosome segregation.
- 12:26And so one of our ideas is to take some
- 12:29of these genes and then manipulate
- 12:31their expression.
- 12:32That is if you have genes whose
- 12:34role in the cell?
- 12:35Is to protect the fidelity
- 12:38of chromosome segregation,
- 12:39then maybe over expressing some of
- 12:41these genes would further protect the
- 12:44fidelity of chromosome segregation
- 12:45and decrease the number of errors
- 12:48that occur during aging.
- 12:49That's some of the research that
- 12:50we plan to do in my lab,
- 12:53and so when you talk about chromosome
- 12:56segregation just to remember back
- 12:58to you know junior high biology,
- 13:01that's that's really when the the cells are
- 13:04replicating and they're going to divide.
- 13:07That your body kind of the cell puts
- 13:09half the chromosomes in one daughter
- 13:11cell and half the chromosomes and the
- 13:14other daughter cell is that right?
- 13:16Yep, the the magic of the cell cycle
- 13:19and so and so is the concept of aneuploidy.
- 13:22When you say that there may be a lack
- 13:25of fidelity that that segregation
- 13:28processes where you know they may
- 13:31put 2047 chromosomes in one cell
- 13:35and and and 45. And the other.
- 13:39Yep, so during the cell cycle
- 13:42you have 46 chromosomes.
- 13:43Normally in most cells in your
- 13:46body during the cell cycle,
- 13:48each chromosome gets replicated and so
- 13:51you wind up with 92 chromosomes instead
- 13:55of 46 for a short period of time,
- 13:58and then those 92 chromosomes need
- 14:00to divide equally such that one
- 14:03daughter cell gets 46 chromosomes
- 14:05and the other daughter cell.
- 14:07Also gets 46 chromosomes and if
- 14:10you have an error in that process
- 14:13and one daughter cell gets 47
- 14:15and the other gets 45 instead,
- 14:18that that produces aneuploidy,
- 14:19that's a chromosome segregation error
- 14:21that we think can have pretty profound
- 14:24consequences for cancer development.
- 14:27Well, we're going to take a short
- 14:29break and learn more about the
- 14:31causes of cancer progression and
- 14:34therapeutic vulnerability right
- 14:35after we take a short break.
- 14:37For a medical minute,
- 14:39please stay tuned to learn more
- 14:41with my guest Doctor Jason Shelter
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- 15:52yalecancercenter.org you're listening
- 15:53to Connecticut Public Radio.
- 15:56back to Yale Cancer answers.
- 15:57This is doctor in East Tag part
- 15:59and I'm joined tonight by my
- 16:01guest Doctor Jason Shelter.
- 16:03We're learning about his research
- 16:05into the genomic causes of cancer
- 16:07progression and before the break
- 16:09Jason you were talking a lot
- 16:12about this concept of aneuploidy.
- 16:13The the idea that having an
- 16:16incorrect number of chromosomes can
- 16:18predispose to cancer and some of
- 16:20the work that your lab is planning
- 16:23on doing to kind of address.
- 16:25That and and look at whether that is a
- 16:28potential target for cancer prevention.
- 16:30But are there other mechanisms of
- 16:34cancer development outside of aneuploidy,
- 16:38that your lab is also looking at?
- 16:40Yep, so in addition to the chromosome
- 16:43errors that occur in cancer,
- 16:45there are single base pair changes
- 16:48point mutations in the sequence
- 16:51of the chromosomes themselves,
- 16:53which have a fundamental role in
- 16:56driving cancer development and at
- 16:58the same time which also create
- 17:01potential therapeutic vulnerabilities
- 17:03or potential ways for scientists
- 17:05and clinicians to treat cancer so
- 17:08so tell us more about that.
- 17:09Maybe give us an example of some
- 17:10of the things that your lab.
- 17:12Is working on in that vein,
- 17:14Yep, so there has been an absolute
- 17:17revolution in cancer therapy over
- 17:19the past 10 to 20 years previously.
- 17:22For most of the 20th century,
- 17:24the standard way to treat cancer was
- 17:27slash and burn was to cut it out of
- 17:30your body through surgery and then
- 17:33to burn any cells that remained
- 17:35with the use of radiation which
- 17:37does kill cancer cells but can have
- 17:40very profound side effects as well.
- 17:42Or with chemotherapy agents,
- 17:44which again can kill cancer cells,
- 17:46but have some pretty significant side
- 17:48effects as well in the past 20 years,
- 17:51there's been a revolution in the
- 17:53development of what are called
- 17:55targeted therapies.
- 17:56That is, these are drugs,
- 17:58which instead of just nonspecifically
- 18:02killing kind of all cells that it encounters,
- 18:05targeted therapies are designed
- 18:07to inhibit specific proteins that
- 18:10are expressed by cancer cells.
- 18:13In order to eliminate cancer
- 18:15cells while leaving normal tissue
- 18:18unharmed or relatively unharmed,
- 18:20my lab uses a genetic tool called
- 18:24crisper and crisper is a new tool for
- 18:28genome engineering that was recently
- 18:31developed just in the past seven or so years,
- 18:35and it allows you to make very precise
- 18:39modifications in the in any cells
- 18:42that you're interested in studying.
- 18:44So using CRISPR you can go into a
- 18:47cancer cell or a normal cell growing
- 18:49in a Petri dish or growing in a mouse.
- 18:52And then you can cut out a gene of interest.
- 18:55Or you can introduce a mutation
- 18:58into a gene of interest and then
- 19:00study how cutting out that gene
- 19:03or introducing a mutation affects
- 19:06the biology of those cancer cells.
- 19:09We can link this then to the question of
- 19:12targeted therapy because we can delete.
- 19:14A gene in cancer cells using crisper.
- 19:17That is,
- 19:17we can knock it out from cancer
- 19:19cells and then we can ask whether
- 19:21these cancer cells live or whether
- 19:23these cancer cells die.
- 19:24So just out of curiosity,
- 19:27when you said that we couldn't do this
- 19:29before CRISPR in mammalian cells,
- 19:31we could only do it in single
- 19:34celled organisms. Why is that?
- 19:36What is how exactly does CRISPR work to
- 19:40allow you to do this in mammalian cells?
- 19:42What's the difference in
- 19:44single celled eukaryotes?
- 19:46You can introduce foreign genetic
- 19:49material quite easy and the cells will
- 19:54oftentimes incorporate the foreign
- 19:56genetic material into their own DNA.
- 20:00They randomly will pick up
- 20:02DNA from the environment and
- 20:04incorporate it into their genomes,
- 20:06and that's in fact unrelated to what I study.
- 20:09But one of the causes of the problem of
- 20:13antibiotic resistance among bacteria.
- 20:16And among eukaryotic parasites
- 20:18that they have this habit of just
- 20:21picking up random DNA and taking it,
- 20:23scientists have taken advantage of
- 20:26that process in order to genomically
- 20:29modify these single celled eukaryotes
- 20:32to study them in the lab.
- 20:35In the context of cancer,
- 20:37cancer cells normal cells don't
- 20:39really do that.
- 20:41Any one of us could take a bath
- 20:43in a pool full of DNA,
- 20:45and we would not start expressing random
- 20:48things from the DNA that we're swimming in.
- 20:51That just isn't how mammalian cells work.
- 20:54Crisper is a DNA cutting enzyme,
- 20:59and so while you normally wouldn't just
- 21:03randomly change or randomly modify DNA.
- 21:07In a eukaryote in a mammalian cell.
- 21:10Because CRISPR is a DNA cutting enzyme
- 21:12we can use it in order to cut the DNA
- 21:15in a certain place in a defined manner,
- 21:18which allows scientists to make
- 21:20these modifications and cancer
- 21:22cells that we couldn't before.
- 21:24When you use crisper say in in a mouse,
- 21:29does it affect all the cells in that
- 21:32mouse or is it a given cell or is
- 21:35it a few cells like how diffuse?
- 21:37Is the effect that you can
- 21:40have on a given gene? Yeah,
- 21:43so it depends on how you use it
- 21:46and how you plan your experiment.
- 21:49CRISPER is useful both as a research
- 21:53tool and itself as a potential
- 21:56therapeutic modality in the future.
- 21:59So in my lab we use CRISPR
- 22:01as a research tool.
- 22:02We want to make certain modifications
- 22:04in cancer cells in order to
- 22:06respond to see how cancer cells.
- 22:08Respond in addition to that,
- 22:11when you start thinking about using
- 22:13crisper in a mouse or in an Organism,
- 22:15there are potential therapeutic
- 22:17uses for CRISPR as well,
- 22:19say to treat genetic diseases
- 22:21or to treat cancer itself.
- 22:23This is much more preliminary.
- 22:25There is a lot of work to do there,
- 22:28but for instance in some of the clinical
- 22:31trials that have been done and in some
- 22:33of the mouse work that has been done,
- 22:35the liver is the organ in your body.
- 22:39That generally detoxifies
- 22:40foreign matter that you receive,
- 22:44and so if you just inject CRISPR
- 22:47particles into a mouse's body,
- 22:50or into a human body,
- 22:52they oftentimes go to the
- 22:54liver and they will genetically
- 22:55modify cells in the liver.
- 22:58So so tell us a little bit more about
- 23:01you know you mentioned that your lab
- 23:04is using CRISPR to kind of figure out
- 23:07targets for potential cancer therapeutics.
- 23:12How do you take that to the next level
- 23:15and figure out what are those targets?
- 23:18How you might design drugs against them,
- 23:21and tell us a little bit more about
- 23:23the potential for this in the future.
- 23:26Yep, so 22,000 genes in the genome.
- 23:29Some of them may make good targets
- 23:31for cancer, and some of them may
- 23:33not make good targets for cancer.
- 23:35The first step in this process is the
- 23:37one that my lab is most active in.
- 23:39We try and use CRISPR to identify
- 23:42the genes and cancer cells that
- 23:44are required for cancer growth.
- 23:47If you can eliminate a gene with CRISPR
- 23:50and it causes cancer cells to die,
- 23:53then that gene might be a promising
- 23:56target for therapeutic development.
- 23:58when it comes to actually
- 24:01developing a drug against that gene,
- 24:04that is a complicated process that we
- 24:07are still learning a whole lot about.
- 24:10There are some genes in the
- 24:12genome which code for proteins.
- 24:15Proteins are the functional part of the cell.
- 24:17The part that actually does the work.
- 24:19There are some proteins that are
- 24:22basically like big greasy balls.
- 24:24They just are greasy and they don't
- 24:26bind to anything and they're very
- 24:28hard for something to latch onto.
- 24:31And something that's you know big
- 24:33and greasy like that just doesn't
- 24:35make a good drug target because there
- 24:38is nothing for a drug to bind onto.
- 24:41What you really want for a drug
- 24:43target is you want a protein that's
- 24:45the part of the cell that that
- 24:47actually does the work that has say.
- 24:51Various binding pockets on it or
- 24:54holes in it where you can design a
- 24:57small molecule compound to actually
- 24:59bind in that pocket and then inhibit
- 25:02that proteins function.
- 25:03So there are some genes that are
- 25:05required for cancer growth but that
- 25:06are very very hard to generate drugs
- 25:08against because they're just greasy
- 25:10and there's nothing to bind onto.
- 25:11And then there are other proteins
- 25:14and cells that are possible for
- 25:16you to design drugs against and
- 25:18we want to see if we can identify
- 25:20those proteins in particular.
- 25:23And so you know, this kind of brings
- 25:25me back to the question that we were
- 25:27talking about earlier in terms of,
- 25:29you know I I get the whole concept of
- 25:32crisper being used to look at jeans
- 25:34that you can specifically target
- 25:36to see whether they would be a good
- 25:39target or a not so good target.
- 25:41But ultimately when you're looking
- 25:43at developing drugs,
- 25:44it sounds like you're developing
- 25:47drugs against proteins.
- 25:48Which brings me back to if you know
- 25:51that a particular gene is involved in cancer,
- 25:54Genesis, uhm, why not target the gene so,
- 25:58especially if crisper is very
- 26:01specific for a particular gene,
- 26:04do you think that that I,
- 26:06I realize you said that earlier
- 26:08that this is very preliminary,
- 26:09but do you think that there will be a
- 26:13role for that kind of gene editing?
- 26:16And can you really do that in?
- 26:18A fully mature adult Organism?
- 26:21Yeah, that's a great question and I
- 26:25think that you're just thinking about
- 26:2725 years in the future right now.
- 26:30So like I to go back to the
- 26:33analogy or the thought experiment
- 26:36that I previously mentioned.
- 26:38If you or I were to dive
- 26:41into a bath full of DNA,
- 26:44nothing would really happen to us because
- 26:47mammalian cells do not readily take.
- 26:50Foreign DNA DNA,
- 26:52as itself is highly charged
- 26:56deoxyribonucleic acid.
- 26:57It it it is an acid and it it won't just
- 27:02normally pass from outside ourselves
- 27:04or outside our body into our body.
- 27:07In order to have.
- 27:11To have crisper actually enter our body,
- 27:15you need to develop some approach
- 27:18that allows a very big macromolecule
- 27:21with a nucleic acid component,
- 27:24because part of crisper
- 27:26is is ribonucleic acid.
- 27:27Actually you need to get that from
- 27:30out of your body into your body and
- 27:33into cancer cells and that problem
- 27:35of delivery getting the crisper
- 27:37where you want it is a pretty
- 27:39significant challenge right now.
- 27:42With current targeted therapies and cancer,
- 27:44these are small molecules.
- 27:46You know, maybe 50 atoms,
- 27:49a hundred 150 atoms and they will pass
- 27:53through cell membranes quite readily,
- 27:56and so it's much easier to get them
- 27:58to cancer cells where they can do the
- 28:01work of inhibiting cancer cell growth.
- 28:03At the same time as we develop
- 28:07improved techniques to get nucleic
- 28:10acids into the body,
- 28:13for instance.
- 28:14People I'm sure are familiar with
- 28:16the M RNA vaccines for COVID-19,
- 28:19which involved getting nucleic acids
- 28:21into cells in your body as those
- 28:25types of approaches for delivery
- 28:27improve will have ways to use
- 28:29CRISPR for cancer treatment as well.
- 28:32Doctor Jason Shelter is an assistant
- 28:35professor of surgery and oncology
- 28:36at the Yale School of Medicine.
- 28:38If you have questions,
- 28:40the address is cancer answers at
- 28:42yale.edu and past editions of the
- 28:44program are available in audio and
- 28:46written form at Yale Cancer Center Org.
- 28:49We hope you'll join us next week to
- 28:51learn more about the fight against
- 28:52cancer here on Connecticut Public
- 28:54radio funding for Yale Cancer
- 28:56Answers is provided by Smilow
- 28:57Cancer Hospital and Astra Zeneca.