Molecular Mechanisms of Cancer
March 28, 2022Information
March 27, 2022
Yale Cancer Center
visit: http://www.yalecancercenter.org
email: canceranswers@yale.edu
call: 203-785-4095
ID7619
To CiteDCA Citation Guide
- 00:00Funding for Yale Cancer Answers is
- 00:02provided by Smilow Cancer Hospital.
- 00:06Welcome to Yale Cancer answers with your
- 00:09host doctor in East JGP are Yale Cancer
- 00:12answers features the latest information
- 00:13on cancer care by welcoming oncologists
- 00:16and specialists who are on the forefront
- 00:18of the battle to fight cancer this week.
- 00:21It's a conversation about the molecular
- 00:23mechanisms of cancer with Doctor Daryl Klein.
- 00:25Doctor Klein is an assistant professor of
- 00:28pharmacology at the Yale School of Medicine,
- 00:30where Doctor Chad Power as a
- 00:32professor of surgical oncology.
- 00:35So Darrell maybe we can start
- 00:36off by you telling us a little
- 00:38bit more about yourself and
- 00:40what it is exactly that you do.
- 00:42Yeah, I mean I think.
- 00:44My path to become a medical
- 00:47researcher involves my personal back
- 00:49story and my love of competition.
- 00:53In some ways, I feel like I've been
- 00:55destined to study kinases and cancer and
- 00:57their mechanisms and and with the hope of
- 01:01developing useful cancer therapeutics.
- 01:02And my career trajectory if you will.
- 01:05As a medical scientist,
- 01:07began long before my formal training.
- 01:10I grew up in New Jersey just outside
- 01:13of Philadelphia, and at a young age.
- 01:15My my sister was diagnosed with cancer.
- 01:18Kimberly, my sister, was diagnosed
- 01:21with MLE or chronic myeloid leukemia.
- 01:25It's a blood cancer that's rare
- 01:28in children at that time.
- 01:31Over 40 years ago now,
- 01:33Peter Noel at the University of
- 01:35Pennsylvania in Philadelphia was studying
- 01:38the driving mutations that lead to CML.
- 01:41And he discovered a chromosome alteration
- 01:43that he dubbed the Philadelphia
- 01:45chromosome and kmle patients,
- 01:47like my sister and and the results
- 01:50of that change.
- 01:51Is that a new protein is made a fusion
- 01:53of a tyrosine kinase signaling protein?
- 01:56That's that's stuck in the on position,
- 01:59and that instructs cells to.
- 02:01To divide and grow and thus cancer.
- 02:04And that protein became a target for
- 02:06drug discovery and it really heralded
- 02:08the era of precision medicine that
- 02:11is specifically targeting a single.
- 02:13You know bad protein with a drug and
- 02:15that and that was really exciting.
- 02:17And in 2001 there was this huge success with.
- 02:20The mat neighbor or Gleevec,
- 02:22and that became the first drug
- 02:25that was developed to target a
- 02:26specific kinase to treat a disease,
- 02:28and in this case, someone.
- 02:30And patients treated with this drug can
- 02:33live long lives with controlled disease.
- 02:36Unfortunately for you know, Kimberly,
- 02:39my sister, at that time it was.
- 02:40It was just the beginning of
- 02:43understanding this disease.
- 02:44And there were no therapeutics,
- 02:46and that meant you know,
- 02:47little could be done, and.
- 02:49In this powerlessness drives me to find
- 02:51ways to spare other families similar
- 02:53devastation and to better understand cancer.
- 02:57You know,
- 02:58I really have spent a large part of my career
- 03:00investigating the molecular basis for,
- 03:03for oncogenic signaling.
- 03:04And.
- 03:05You know on that path I attended
- 03:08the University of Pennsylvania
- 03:10for my undergrad in my PhD,
- 03:13and my medical degree,
- 03:14and I did clinical rotations at the
- 03:17Children's Hospital of Philadelphia Chop.
- 03:19So I was walking the same halls as Peter,
- 03:22Noel and my parents and my
- 03:25sister years before.
- 03:26I joined the MSTP or medical
- 03:29Scientist training program and.
- 03:31This was funded by the NIH,
- 03:33the National Institutes of Health,
- 03:35to grant to train a group of physicians,
- 03:38also to be researchers,
- 03:39and the goal of that program is
- 03:41basically to link basic science
- 03:43findings to the clinic.
- 03:45The bench to the bedside and to
- 03:48Brig lab progress into useful
- 03:51therapeutics as rapidly as possible.
- 03:53And I think the success of Leave Act was
- 03:56just the beginning of targeting kinases.
- 03:58These these tires and kinases
- 04:00other kinases and cancer.
- 04:02And so when I was at Penn,
- 04:04I studied under Professor Mark Lemon.
- 04:07He was working on those other kinases
- 04:09that lead to different cancers.
- 04:11And you know, to see how they might
- 04:14cause cancer and how we might leverage
- 04:17understanding their mechanisms
- 04:18to develop new therapeutics.
- 04:22I also mentioned you know my my
- 04:25desire for you know competition.
- 04:29And so one thing I I'm not sure
- 04:31that people really understand is
- 04:34how competitive research compete.
- 04:36And I, you know,
- 04:37I grew up playing sports in college
- 04:39and I love competing and and track and
- 04:41field and crew and football and baseball.
- 04:43And when I first joined Mark's
- 04:46lab at Penn and and was first
- 04:48introduced to lab research,
- 04:49I realized there that.
- 04:51Scientific researches is intensely
- 04:53competitive and I think it makes Olympic
- 04:56sport seem safe by comparison and and I
- 04:59love that and I loved everything about that.
- 05:03And then the problem is in
- 05:05sensually in science.
- 05:06You're competing with unknown
- 05:08competitors and and an unknown number
- 05:11of of teams and and the rules of the
- 05:14game are undefined and you don't even
- 05:16know when the conversation started.
- 05:18So,
- 05:18and certainly your competitors have
- 05:20more money and resources than you do,
- 05:22so you're always the underdog and and
- 05:25that excites me and I and I like that.
- 05:28You know an example.
- 05:29When we started the project will chat
- 05:31more about in a in a little bit.
- 05:33We were certain that that you know
- 05:35half a dozen other groups in the world
- 05:38were already working on it and and we
- 05:40didn't know how far along they were.
- 05:42And so all you know is what you don't know.
- 05:44And if you want to win,
- 05:46you have to work nonstop like 24/7.
- 05:48I once spent 50 hours straight in the lab
- 05:52when I was a grad student without sleeping.
- 05:54And then you know that was exciting to me.
- 05:57That's something you can't do in.
- 06:00In sport after the game you you go home,
- 06:03but science is a years long competition
- 06:06with no timeouts and and the
- 06:08intensity is is off the charts so.
- 06:12I think that that frames kind of.
- 06:14Why I became a medical researcher
- 06:17and and and why?
- 06:19Why I love doing the work that I do.
- 06:23So let's take a step back for a bit.
- 06:25I mean, that sounds really inspiring
- 06:28and and interesting in terms of
- 06:30how this kind of came full circle.
- 06:32How you? Had this experience
- 06:34with your sister and then went on
- 06:37to to become a scientist that's
- 06:39hopefully making a difference in the
- 06:41lives of other patients like her.
- 06:43But for our audience,
- 06:45maybe you can take a step back and
- 06:48tell us exactly like what is a kinase
- 06:51and why are they important in cancer?
- 06:54Sure, sure, yeah.
- 06:56I mean I should also mention
- 06:58that while I trained as A and
- 07:00MDP MD PhD physician scientist,
- 07:03I've actually chosen a path
- 07:06devoted entirely to research.
- 07:08So during training, when I you know,
- 07:11find myself engaging with patients
- 07:13and and talking to them about the
- 07:16unfortunately limited treatment options I,
- 07:17I found that difficult and frustrating
- 07:19and and all I wanted to do was rush
- 07:21back to the lab and and and find
- 07:24new potential therapeutic avenues.
- 07:25So I made a choice to devote
- 07:27myself entirely to lab work,
- 07:29but at the same time I'm still
- 07:31working with other physicians,
- 07:33scientists and clinicians to
- 07:34help bridge our our discoveries.
- 07:37To the bedside.
- 07:39Kinases are often drivers of
- 07:43cancers and and the one that I've
- 07:45been working on recently ALK and
- 07:48a plastic lymphoma kinases is a
- 07:50well known cancer related protein.
- 07:53And much like the protein involved
- 07:55in my sisters of Mle,
- 07:57it's a tyrosine kinase and
- 07:59basically tyrosine kinases instruct
- 08:01the cells to grow and divide,
- 08:04and if this is unregulated
- 08:07that leads to cancer.
- 08:10So ALK well, unlike the Siml case, ALK is.
- 08:15Is A is a receptor tyrosine kinase.
- 08:18So what that means is ALK is
- 08:20located in a different part of
- 08:22the cell than the CML kinase.
- 08:24So if it if a cell were an ocean,
- 08:27the CML kinase would be a submarine
- 08:30and ALK would be more like an aircraft
- 08:33carrier at the surface and so this.
- 08:36Localization difference has
- 08:38therapeutic implications.
- 08:39As you might imagine,
- 08:40you can't target a submarine the same
- 08:42way you would target in an aircraft carrier.
- 08:44So in the clinic we use small molecule.
- 08:47You know missile like drugs that can dive
- 08:49deep into the ocean to reach that kmle.
- 08:52Kinase submarine whereas for ALK we
- 08:54have an opportunity to use antibodies
- 08:57that can target it at the cell surface,
- 09:00so more like a.
- 09:01You know a B52 bomber.
- 09:05It's been known for years that
- 09:07ALK is a driver of neuroblastoma.
- 09:09Now neuroblastoma is a cancer of
- 09:12the peripheral nervous system.
- 09:15It's one of the more common pediatric
- 09:17cancers that accounts for more than
- 09:1910% of childhood cancer mortality.
- 09:23But clinically useful therapeutics
- 09:26have been slow to develop,
- 09:29and I think you know one of the key
- 09:32reasons for this slow development of
- 09:34treatments is likely the lack of a.
- 09:36Structural framework for the target alcc.
- 09:39Simply put,
- 09:40we have you know no idea what it
- 09:42looked like or how it functioned.
- 09:44It was a a complete mystery before our work.
- 09:47I mean the fact that ALK is expressed on
- 09:51neuroblastoma cells but is not present.
- 09:53On healthy tissue makes Alka
- 09:56veritable oncogenic beacon.
- 09:58That's a perfect target
- 10:01for precision medicine.
- 10:02It's much like the novel
- 10:04fusion protein and kmle.
- 10:06In each case the protein.
- 10:10Specifically,
- 10:10if you're targeting the protein specifically,
- 10:12it should have little side effects
- 10:14outside of the cancer itself.
- 10:16And the hope is that if we can target
- 10:19this kinase alken neuroblastoma.
- 10:22That we might have the same positive
- 10:25outcomes for neuroblastoma that
- 10:26we see for patients with KMLE.
- 10:29So you know one of the things that
- 10:32always fascinates me is how you
- 10:34find these things to begin with.
- 10:36I mean, how do we know that these
- 10:39kinases play a role in cancer?
- 10:41How does that? How do you figure that out?
- 10:44How do you know which kinases are
- 10:47submarines and which kinases are
- 10:49our aircraft carriers, I mean.
- 10:52And how did you figure out that
- 10:55these were important anyways?
- 10:57How does that happen?
- 11:00That's a good question.
- 11:01That's certainly outside
- 11:02of my lab's expertise.
- 11:07A lot of that is done through genomic
- 11:10work and associating certain genes
- 11:14with certain disease phenotypes,
- 11:17and so where my labs expertise
- 11:19comes in pretty much after the fact.
- 11:22Once these associations are known.
- 11:26That's where we come in to help define
- 11:29bio physically and structurally,
- 11:31exactly how these kinases
- 11:33and uncle genes are acting,
- 11:36and hopefully if we have a molecular
- 11:38picture of that how we might design
- 11:41and develop therapeutics to.
- 11:43To stall that and and prevent disease.
- 11:48So when you say that it it kind of all
- 11:51starts with understanding what genes
- 11:53are expressed in what genes aren't.
- 11:56I mean it, it sounds like the progress
- 11:59that we make in terms of cancer
- 12:03medicine is really investigators.
- 12:05Building on other investigators
- 12:07building on other investigators work.
- 12:10So somebody you know maybe was sequencing
- 12:12some genes and found that some genes were
- 12:16overexpressed in some cancers versus not.
- 12:19And then other people kind of discovered that
- 12:22that gene was associated with a protein like.
- 12:25A kinase and then you look at
- 12:28that kinase and say well where
- 12:30is it and how can we target it?
- 12:32Is that kind of how that works?
- 12:35That's
- 12:35exactly right, right? I mean,
- 12:37it's it's work of a tremendous number
- 12:40of individuals with differing expertise.
- 12:44Certainly the approach my lab takes
- 12:46is just one cog in that machine,
- 12:49one that's a bit further down,
- 12:51and probably less than the discovery stage.
- 12:52But one one that is keenly
- 12:55important to understand the
- 12:56mechanism of how molecules work,
- 12:59which can then give us insight
- 13:01into how we might target these
- 13:03and develop therapeutics.
- 13:04Around their function.
- 13:07And then the other question
- 13:09that that I often have is.
- 13:11OK, so you know you discover this kinase and
- 13:15you discover that it's important in cancer.
- 13:19Why is it that some kinases are important
- 13:22in some cancers but not in others?
- 13:25I mean, how do these kinases?
- 13:27Why? Why do you have these genes
- 13:30for these kinases to begin with?
- 13:33And why are they differentially expressed?
- 13:37Cancer often recapitulates the the paradigms
- 13:42that are important and during development.
- 13:47So all of these kinases are crucially
- 13:49important in the in the stages of development
- 13:53and help patterning and complex tissues.
- 13:56After that, they they often kind of
- 13:59are aren't used so much in adulthood,
- 14:02and it's only during cancer.
- 14:04In the the oncogenic process that a lot of
- 14:08these developmental pathways are reawakened,
- 14:12and they can be reawakened in different
- 14:14tissues and and different places,
- 14:16but they all.
- 14:17Lead to the same thing.
- 14:19Basically once you turn return
- 14:21a kinase on your turning on
- 14:24the the growth instructions and
- 14:27when that's not counterbalanced,
- 14:30that's how cancer develops.
- 14:33Well, we're going to take a
- 14:34short break for a medical minute,
- 14:36but when we come back,
- 14:38let's learn more about the molecular
- 14:40mechanisms of cancer and how exactly
- 14:43we target these differentially
- 14:44expressed kinases to actually
- 14:46make a difference for patients,
- 14:49please stay tuned for more with
- 14:51my guest doctor Daryl Klein
- 14:53funding for Yale Cancer Answers comes
- 14:55from Smilow Cancer Hospital with an
- 14:58event focused on nutrition for cancer
- 15:00survivorship presented by the Smilow
- 15:02Cancer Care Center in Trumbull.
- 15:04April 14th Register at Yale Cancer Center.
- 15:07Org or email cancer answers at Yale.
- 15:12The American Cancer Society
- 15:14estimates that nearly 150,000 people
- 15:16in the US will be diagnosed with
- 15:19colorectal cancer this year alone.
- 15:21When detected, early colorectal cancer
- 15:23is easily treated and highly curable,
- 15:26and men and women over the age of
- 15:2845 should have regular colonoscopies
- 15:30to screen for the disease.
- 15:32Patients with colorectal cancer
- 15:33have more hope than ever before,
- 15:35thanks to increased access to advanced
- 15:38therapies and specialized care.
- 15:40Clinical trials are currently
- 15:42underway at federally designated
- 15:44Comprehensive Cancer Centers.
- 15:45Such as Yale Cancer Center and its Milo
- 15:48Cancer Hospital to test innovative new
- 15:51treatments for colorectal cancer tumor.
- 15:53Gene analysis has helped improve
- 15:55management of colorectal cancer
- 15:57by identifying the patients most
- 15:59likely to benefit from chemotherapy
- 16:02and newer targeted agents,
- 16:03resulting in more patient specific treatment.
- 16:06More information is available at
- 16:09yalecancercenter.org you're listening
- 16:11to Connecticut Public Radio.
- 16:13Welcome back to Yale Cancer answers.
- 16:15This is doctor in East Egg
- 16:16part and I'm joined tonight by
- 16:18my guest doctor, Daryl Klein.
- 16:19We're learning more about the molecular
- 16:22mechanisms of cancer and right before
- 16:24the break Daryl was telling us about
- 16:26this profoundly inspiring story of
- 16:28his sister who is diagnosed with CML,
- 16:30which really started his journey
- 16:32on becoming a physician scientist,
- 16:34and one who is particularly interested
- 16:37in these molecules called kinases,
- 16:41which really work.
- 16:43To activate the growth of of cancer
- 16:48cells and so you know Darrell before
- 16:51the break you were mentioning that
- 16:54eurolab really after we know that
- 16:57you know a kinase is involved in a
- 17:00particular cancer is really involved
- 17:03in looking at its its structure
- 17:06and kind of how to target it.
- 17:08Is that right?
- 17:10Exactly,
- 17:12my lab is a structural biology lab,
- 17:15so you know, we're sensually photographers.
- 17:18But we take pictures of of very,
- 17:20very tiny things, molecules and proteins,
- 17:24and so this. Requires specialized
- 17:26equipment cameras if you will.
- 17:28That use X rays and electrons rather
- 17:32than light in the in the visual
- 17:35spectrum that that we're used to.
- 17:37Uhm? You know, many people know.
- 17:40DNA, so let's start there.
- 17:42People have heard of DNA and Watson
- 17:45and Crick and and they're double Helix.
- 17:48And DNA is is basically a cookbook
- 17:51with 10s of thousands of recipes,
- 17:54and they're mostly protein recipes,
- 17:57so I guess it's a keto or Paleo cookbook.
- 18:02ALK is one of these recipes.
- 18:05And the recipe in the DNA cookbook tells us
- 18:08the ingredients and the order to make alcc.
- 18:12But one big problem with this DNA cookbook.
- 18:17Is it's not illustrated,
- 18:18so we have no idea what the
- 18:21final product will look like.
- 18:23So you know my lab follows the recipe to
- 18:26take pictures of the final products to.
- 18:29To illustrate this, this DNA cookbook.
- 18:32So we take molecular photographs
- 18:35of the protein and also the mutants
- 18:39that are found in cancer.
- 18:41And in these pictures give us a better
- 18:44understanding of of how things supposed
- 18:46to look like and how it changes in cancer.
- 18:49And in this can inform us
- 18:52about approaches to.
- 18:53Designing targeted therapeutics.
- 18:58So my lab just reported the structure
- 19:01of of the protein ALK in nature.
- 19:05That's the tyrosine kinase that's
- 19:08important in neuroblastoma.
- 19:10And this gave us a first look at
- 19:13this unique uncle Gene and it's,
- 19:16you know it's going to be impossible
- 19:18for me to relay the complexities here.
- 19:21But if we stick to our.
- 19:23Analogy of the the cell is an ocean, it's.
- 19:26It's not unreasonable to say that
- 19:28Alcc did actually look a bit like an
- 19:31aircraft carrier. I mean it had this.
- 19:34Unusual a long gated structure and it
- 19:37probably lies parallel to the to the surface,
- 19:41so it's like an aircraft carrier
- 19:43floating on the water.
- 19:44Or the surface of a cell.
- 19:47And and furthermore,
- 19:48we can see how it actually gets activated.
- 19:52Basically two of these aircraft carriers
- 19:55line up next to one another and in
- 19:58that position they're then capable to
- 20:00sell to send their their growth signals,
- 20:03which ultimately end up being
- 20:05cancerous growth signals.
- 20:06To the neuroblastoma cell.
- 20:09Uncontrolled ALK activation like
- 20:11this leads to cancer and it and it
- 20:14results from the tumor continuing to
- 20:16express this developmental out gene
- 20:19along with its stimulatory ligand.
- 20:24Our research reveals an approach
- 20:26to shutting off ALK and and that
- 20:29it can be quite straightforward.
- 20:31Potentially if we use our structure
- 20:35as a as a blueprint,
- 20:36we can see clear areas where
- 20:38we would want to target this.
- 20:40This aircraft like molecule.
- 20:41I mean there's certain vulnerabilities
- 20:44that are revealed in the structure that
- 20:46we can strategically target and and
- 20:48you know sync this aircraft carrier,
- 20:50and so my lab now is designing potent
- 20:53antibodies. That specifically
- 20:55target these regions in ALK,
- 20:58and you know there's there's small
- 21:00molecules currently out there in use for.
- 21:02Neuroblastoma, as well as many other
- 21:05different cancers that are driven or
- 21:07or partially dependent on on kinases.
- 21:11And compared to small molecule
- 21:13therapeutics antibodies,
- 21:14I think can offer a great benefit.
- 21:17The small molecule drugs that
- 21:19are now currently in use like
- 21:22prison and and learn Latin.
- 21:24They target the intracellular.
- 21:25The actual kinase domain of the protein out.
- 21:29And one problem with these types of
- 21:32inhibitors is that you can't keep
- 21:34fooling the cancer for very long.
- 21:35They the cancer figures out this
- 21:37trip quite fast that you're trying
- 21:39to inhibit it in this in this domain,
- 21:42and they and the cancer makes changes
- 21:45that diminish the drugs impact.
- 21:47Whereas I think the antibody
- 21:49approach is is is a more brute
- 21:52force approach and it's harder for
- 21:54the cancer to overcome this,
- 21:55the strategy of inhibition.
- 21:57I think the the therapeutic future
- 22:00will likely use a combination
- 22:02of these two to completely.
- 22:05Dismantle the the out machinery.
- 22:09In some ways you know cancer can be
- 22:11feod viewed as having some of the
- 22:13similar challenges that we see for SARS,
- 22:15Co V2 and both use similar
- 22:18strategies to overcome disease.
- 22:20Both you know cancer and
- 22:23viruses mutate rapidly.
- 22:25And they can evolve to
- 22:28different inhibitor approaches.
- 22:30And just as we use antibodies
- 22:32through vaccination or or directly
- 22:35injecting recombinant antibodies and
- 22:38small molecules to overcome COVID.
- 22:41Now we have a new blueprint for ALK to
- 22:44help us overcome similar challenges
- 22:46that are encountered in in cancer
- 22:49and in particular neuroblastoma.
- 22:52And it sounds like when you know the the
- 22:55structure of these aircraft carriers.
- 22:58But you can be very specific about
- 23:00you know targeting those particular
- 23:03molecules as opposed to normal cells.
- 23:06So you might have you know
- 23:08a bomber that only targets,
- 23:11you know that flatbed where the
- 23:13aircraft lands on the aircraft carrier.
- 23:15Or you can have some sort of a.
- 23:19A mechanism whereby these two aircraft
- 23:22carriers can't line up together that really
- 23:25wouldn't apply in any other situation,
- 23:27so you can try to get more precise
- 23:30or more targeted therapies.
- 23:32Is that right?
- 23:34That's exactly right,
- 23:35and remember that I said that you know,
- 23:38since alpha is expressed only
- 23:40on neuroblastoma cells but not
- 23:42present on healthy tissue,
- 23:44it really makes targeting
- 23:46ALK the perfect for you know.
- 23:48Set up for precision medicine
- 23:49and then a layer on top of that,
- 23:52which I think you were just referring
- 23:54to is now that we know the detailed
- 23:57structure and blueprints of this.
- 23:59And that's exactly what we're trying to do.
- 24:00We're trying to design
- 24:02antibodies that specifically.
- 24:04Block areas on the protein that are
- 24:07involved in important for it's activation.
- 24:10That is precisely where the ligand
- 24:13binds to activate the receptor and
- 24:17getting back to how it's activated.
- 24:20Where we see the the two molecules
- 24:23lining up side-by-side to each other,
- 24:25we're designing antibodies that can
- 24:27block that interface to prevent it
- 24:30from being activated that is being
- 24:32activated independent of ligand.
- 24:34Which could be caused by certain mutations,
- 24:36which is further research that we're
- 24:39doing now or or with the ligand.
- 24:42So we're using all this information
- 24:45to specifically design antibodies
- 24:48that are tailored to this molecule
- 24:50and the and the type of mutations
- 24:53or mechanisms that activate it
- 24:56specifically in in neuroblastoma.
- 25:00And so as you design these
- 25:02antibodies in these treatments,
- 25:04you're doing that in the lab. How?
- 25:07How does it actually get into patients?
- 25:09How does it affect people like your sister?
- 25:12Because that's where the story
- 25:14really started and how long
- 25:16does that whole process take?
- 25:20You're right, that's a that's certainly
- 25:22is is a long process and you know
- 25:24Cancer Research is is so matured and
- 25:27specialized now that it really requires
- 25:29you know effort to put these discoveries
- 25:32into usable formats and for others
- 25:34to build upon and meaningful ways.
- 25:37And just as the NIH created that MSTP
- 25:40program to link basic science and patient
- 25:43Care now I think we need similar links
- 25:45between basic science researchers.
- 25:47I mean, the you know RNA biologist
- 25:51and chromosome researcher and.
- 25:52And in the biophysicist like me
- 25:54trying to link up with the model
- 25:57Organism biologist to test the a lot
- 25:59of these and preclinical setups.
- 26:02We all speak a different scientific dialect
- 26:04and we have different perspectives,
- 26:06so you know how do we work together
- 26:11and in one answer to that is is,
- 26:13you know being part of the Yale Cancer
- 26:15Biol Biology Institute that I'm a part of.
- 26:17You know we we really bring
- 26:20together desperate researchers among
- 26:22those interested in cancer.
- 26:24And so you know now I have and and
- 26:26being a physician scientist so you know
- 26:29now there's a cohort of people and
- 26:32colleagues that I can work with that
- 26:35can bring our developing antibodies
- 26:37that we have into preclinical testing
- 26:40quite rapidly to see if they do.
- 26:44So good activity in vivo and then that
- 26:48hopefully can be rapidly leveraged
- 26:50into reaching the the patients that
- 26:53desperately need these treatments.
- 26:57Sounds very much like you
- 26:58had mentioned earlier,
- 27:00but this is kind of a microcosm for
- 27:02the macrocosm of how science works,
- 27:05that that your lab puts together.
- 27:07People who all kind of come at
- 27:09the problem of of ALK from a
- 27:12slightly different vantage point.
- 27:14But the work in your lab kind of builds
- 27:18on the work of other people's labs,
- 27:20and so maybe in in the last
- 27:23few minutes that we have,
- 27:25you could tell us kind of a little bit about.
- 27:27How that works in the grand scheme of things?
- 27:29I mean, it sounds like.
- 27:31One of the things that we've realized with
- 27:33the pandemic is that the world is shrinking,
- 27:35and hopefully the scientific discovery
- 27:38from one lab to another kind of.
- 27:42Bounces around fairly easily.
- 27:43How does that collaboration work?
- 27:46I think it is. It is certainly a challenge
- 27:49and I think you know getting getting
- 27:52researchers to to talk to each other and
- 27:55work together is an important part of that.
- 27:58And like you said, I think you know
- 28:01during the pandemic and having people
- 28:04communicate in different ways like we
- 28:06are now through zoom and other things.
- 28:09Maybe the world is shrinking a bit and I
- 28:11think that's a good thing for science and
- 28:14that's a good thing for research because.
- 28:17Of course, all of us working
- 28:19independently and making advances.
- 28:21We don't want them to go unnoticed
- 28:23by the people next in that chain
- 28:25that you were talking about.
- 28:26That's necessary to make the
- 28:28leap to bring these discoveries
- 28:31to their therapeutic potential.
- 28:33Doctor Daryl Klein is an assistant
- 28:36professor of pharmacology at
- 28:37the Yale School of Medicine.
- 28:39If you have questions,
- 28:41the address is canceranswers@yale.edu
- 28:43and past editions of the program
- 28:45are available in audio and written.
- 28:47Farm at yalecancercenter.org.
- 28:49We hope you'll join us next week to
- 28:52learn more about the fight against
- 28:53cancer here on Connecticut Public
- 28:55radio funding for Yale Cancer Answers
- 28:57is provided by Smilow Cancer Hospital.