Advancing our Understanding of Gastrointestinal Diseases

Transcript

• 00:00Funding for Yale Cancer Answers is
• 00:02provided by Smilow Cancer Hospital.
• 00:06Welcome to Yale Cancer Answers with
• 00:08your host doctor in Anees Chagpar.
• 00:11Yale Cancer Answers features the
• 00:13latest information on cancer care by
• 00:15welcoming oncologists and specialists
• 00:16who are on the forefront of the
• 00:19battle to fight cancer. This week,
• 00:21it's a conversation about using
• 00:22chemical tools to detect cancer
• 00:24causing proteins with doctor
• 00:26Stavroula Hatzios.
• 00:27Dr Hatzios is assistant
• 00:29professor of molecular,
• 00:30cellular and developmental
• 00:31biology and of chemistry at the
• 00:33Yale School of Medicine where
• 00:35Doctor Chagpar is a professor of
• 00:37Surgical oncology.
• 00:40Maybe we can start off
• 00:42by you telling us a little bit more
• 00:44about yourself and what it is you do.
• 00:47My background is in chemistry
• 00:49and microbiology so not a
• 00:51traditional cancer biologist,
• 00:53but I use chemical tools to better
• 00:56understand infectious diseases and
• 00:58more specifically how microbes can
• 01:01contribute to cancer in humans.
• 01:03So in my training I started out by
• 01:06researching infectious diseases,
• 01:08particularly airborne pathogens.
• 01:10Like Mycobacterium tuberculosis
• 01:12that causes human tuberculosis,
• 01:15but then as a postdoc,
• 01:16I switched to studying
• 01:18gastrointestinal pathogens,
• 01:19principally vibrio cholera,
• 01:20which is the bacterium that causes
• 01:22the diarrheal disease cholera.
• 01:24And it was through my postdoctoral
• 01:26training that I began to engage in
• 01:28conversations with other scientists
• 01:30who recommended that I start applying
• 01:32some of the chemical tools and
• 01:34approaches that I was a developing
• 01:36to study comparatively understudied
• 01:38microbes like Helicobacter pylori.
• 01:40And that was really my entry point into
• 01:43the field of cancer microbiology and
• 01:45cancer microbiology really refers to
• 01:47an area of research that's emerging
• 01:49where we're looking at how microbes
• 01:52that indigenous microbes in our bodies.
• 01:54Which comprise the microbiome,
• 01:56as well as infectious microbes that
• 01:59cause disease might contribute to the
• 02:01development of cancer in humans or
• 02:04alter outcomes of cancer therapies.
• 02:06So I begin researching Helicobacter
• 02:08pylori a little bit as a postdoc,
• 02:09and that's really been the focal
• 02:11point of my labs work.
• 02:12Trying to understand how this very
• 02:15important gastric or stomach pathogen
• 02:17causes cancer in a subset of infected humans,
• 02:21and what are the pathways the
• 02:23molecular events by which cancer.
• 02:25Develops and we use a lot of
• 02:27chemical approaches to sort of
• 02:28understand what those pathways are.
• 02:31Yeah, so I was going to ask
• 02:33something along the same vein.
• 02:35Many people, when they think
• 02:37about Helicobacter pylori or H.
• 02:39Pylori, as it's sometimes
• 02:41known we think about ulcers.
• 02:43We don't really think about cancer.
• 02:45So can you talk a little bit
• 02:47more about the link between H.
• 02:49Pylori and cancer and how how
• 02:51you got started with that?
• 02:54Absolutely yeah, H.
• 02:56Pylori is a fascinating,
• 02:58fascinating microbe.
• 02:59As you mentioned,
• 03:00it is primarily linked,
• 03:02at least in public knowledge,
• 03:04to peptic ulcers, stomach inflammation.
• 03:07But it's also the leading risk
• 03:10factor for gastric cancer,
• 03:11which I think currently remains
• 03:13the third leading cause of cancer
• 03:16related deaths worldwide.
• 03:18This is a microbe that's found
• 03:20in half of the global population,
• 03:22and for most people it it doesn't
• 03:25lead to cancer.
• 03:27It may actually be innocuous,
• 03:29meaning it may not do too
• 03:30much to the infected host,
• 03:32but a subset of those who carry the
• 03:34microbe as a normal part of their
• 03:37stomach microbiome will develop peptic
• 03:39ulcers and gastric inflammation,
• 03:41called gastritis.
• 03:42That's roughly 10 to 15%
• 03:44of people who have H.
• 03:46Pylori and then a much smaller percentage.
• 03:481 to 3% typically go on to develop
• 03:51gastric cancer and this connection
• 03:52was only made a couple of decades ago
• 03:55by Robin Warren and Barry Marshall,
• 03:58who won the Nobel Prize in medicine in
• 04:002005 for this discovery that this microbe.
• 04:03Can cause peptic ulcers,
• 04:05gastric inflammation and ultimately
• 04:07cancer and in fact due to their work, H.
• 04:11Pylori is now the first,
• 04:13formally characterized or classified
• 04:15microbe known to be a human carcinogen.
• 04:19So in individuals who have H.
• 04:21Pylori,
• 04:22the microbe can cause chronic
• 04:26inflammation of the gastric lining
• 04:28and overtime and some hosts.
• 04:29This can develop into gastric cancer.
• 04:33And what's a major challenge for
• 04:35those of us in the field is trying
• 04:37to understand why it is that some
• 04:39individuals develop cancer and others do not.
• 04:42And that's a really important question.
• 04:44The reason it's so important is
• 04:46that typically if someone has H.
• 04:48Pylori.
• 04:48You can administer antibiotics
• 04:50to get rid of microbe,
• 04:53but these microbes have a
• 04:54way of evolving very,
• 04:55very rapidly and thus they
• 04:58they evolve drug resistance,
• 05:00which limits the number of drugs
• 05:01that we have available to treat them.
• 05:03So if you just administer in
• 05:04a biotics to half the global
• 05:06population to rid them of H.
• 05:08Pylori,
• 05:08that may not be the best approach
• 05:10because you'll fuel the rise
• 05:12of antibiotic resistance.
• 05:13And there's also some emerging
• 05:15thought that H.
• 05:16Pylori may actually be beneficial to
• 05:18some portion of the population since.
• 05:20People carry this microbe,
• 05:21usually from childhood,
• 05:22and it can help train the immune
• 05:25system similarly to how we think
• 05:26of other microbes that are found
• 05:28in our microbiome.
• 05:29So trying to understand whom should
• 05:32be treated with antibiotics and
• 05:34when who is at risk of developing
• 05:36cancer down the line.
• 05:37That's a very important question,
• 05:39and that's some of what our work
• 05:40is focused on understanding.
• 05:43So tell us more about that because
• 05:45that that clearly is fascinating
• 05:46when you think about you know so
• 05:48much of the world's population.
• 05:50Have this this bacteria you know
• 05:53a reasonable proportion of them.
• 05:56Get gastritis and ulcers and are
• 05:58typically treated with as you say,
• 06:01antibiotics and acid reducing medications.
• 06:06But there is this subset
• 06:07who go on to get cancer.
• 06:08So what do we know about that population
• 06:11and why it is that they are more
• 06:15susceptible to developing malignancy?
• 06:18Great question I. I think we don't fully
• 06:20know and that's something that a lot
• 06:23of research in the field is focused on.
• 06:25We have some indications as a field as to
• 06:28what might be increasing the risk among
• 06:31certain individuals and those can range
• 06:34from geography to diet to genetic background,
• 06:37but there are challenges also in
• 06:38making some of those associations.
• 06:40So certainly there are certain parts
• 06:42of the world in which the incidence of
• 06:45H pylori associated gastric cancer.
• 06:48Is higher particular parts of South America?
• 06:51For example, there have been studies linking
• 06:54altitude to the risk of developing H.
• 06:57Pylori associated gastric cancer,
• 06:59as well as the amount of salt in
• 07:01the diet as well as iron levels.
• 07:03So various environmental factors
• 07:04are thought to increase risk and
• 07:07certainly genetic predisposition
• 07:08in some cases may play a role,
• 07:10although we don't fully understand
• 07:12what those factors may be.
• 07:14A challenge there is that the
• 07:16microbe is found in such a large
• 07:18portion of the population.
• 07:20That it can be difficult to identify
• 07:22key factors that really predispose
• 07:24subset to the development of cancer
• 07:26risk and on the microbial side,
• 07:28which I haven't really mentioned thus far.
• 07:31The Microbit itself has a very complex
• 07:33evolutionary history which in and
• 07:35of itself is super fascinating.
• 07:37It's thought to have Co evolved with humans
• 07:40since several thousands of years ago,
• 07:43over 60,000 years.
• 07:44It's been with humans and thus the phylogeny.
• 07:47Basically the evolutionary history.
• 07:48How this microbe has evolved.
• 07:50Can be used to trace migratory
• 07:52patterns of the human, the human race,
• 07:55and it's really thought that the
• 07:58microbe evolves quite rapidly as well.
• 08:00Once it's in a specific human host
• 08:03and thus it can be very difficult
• 08:05to assign specific microbial genetic
• 08:08patterns with cancer risk.
• 08:09Although there are,
• 08:10I should note,
• 08:11some important proteins and genes
• 08:14that the microbe carries which
• 08:16do correlate very strongly with
• 08:17cancer risk in some individuals.
• 08:20So, so how do we kind of move that forward?
• 08:26I mean when we think about people who
• 08:29you know present to their doctor with
• 08:32stomach pain and and ulcers and gastritis,
• 08:35they generally speaking will have
• 08:37an endoscopy and a a small biopsy
• 08:40will be taken and sent to the lab
• 08:42and the lab will confirm that.
• 08:44Yes indeed they have H pylori.
• 08:47Is it, you know,
• 08:49given what you just mentioned,
• 08:51is it possible for that lab instead
• 08:53of just saying yes, you have H.
• 08:56Pylori to look at the particular
• 08:58features of of that particular H.
• 09:01Pylori and say well,
• 09:03this particular brand of H.
• 09:05Pylori has an increased risk of you
• 09:09developing gastric cancer versus
• 09:12another brand of the same bacteria.
• 09:17Yes,
• 09:18I do think that that's possible.
• 09:20It is possible to culture the
• 09:23microbes from from human samples
• 09:25and assess at a genetic level
• 09:28if the microbe contains these.
• 09:30These risk factors,
• 09:31and I think that's one possible approach.
• 09:34Practically speaking,
• 09:34it may be a bit challenging,
• 09:36but as we have more advances with
• 09:38regards to genome sequencing and
• 09:40PCR based methods that can help us
• 09:43identify these factors quickly,
• 09:45I think that's one approach.
• 09:46I think what is maybe more important
• 09:49as we move forward in the field is
• 09:52trying to identify early risk factors
• 09:55because maybe one thing I haven't
• 09:57mentioned is that gastric cancer
• 09:59tends to present quite later in life,
• 10:01so with with regards to H.
• 10:03Pylori infection.
• 10:04As I mentioned,
• 10:05children usually are infected with
• 10:07the microbe when they're very young.
• 10:09Typically we believe through
• 10:10household contacts with other family
• 10:12members who have the microbe.
• 10:14And it's not until decades later that
• 10:16someone would present with gastric cancer.
• 10:19So this very there's this very
• 10:20long lag phase from, you know,
• 10:22the infection in childhood to the
• 10:24development of gastric cancer.
• 10:26And once it's diagnosed,
• 10:27it can be pretty late stage.
• 10:30So that's also challenging in
• 10:32terms of treatment.
• 10:33And so I think what's needed
• 10:35are ways to assess much earlier.
• 10:37Whether or not someone is at
• 10:39risk and one way,
• 10:40as you mentioned,
• 10:40could be looking at the microbe
• 10:42and then others.
• 10:43Others may be trying to identify.
• 10:45Host factors that may be indicative
• 10:48of of infections that may be heading
• 10:51down the road towards cancer,
• 10:52and that's what I think a lot of
• 10:54research in this area is focused on,
• 10:56including the work of my own lab,
• 10:57is trying to identify effects that
• 11:00microbes may have on the host
• 11:02that could be translated into new
• 11:04diagnostic tests and indications
• 11:06of early cancer risk.
• 11:08So, so tell us more about that in terms
• 11:11of the work that's going on in your lab,
• 11:14sure, so. What we're trying to do is
• 11:17excuse me, is trying to understand.
• 11:20How infection alters proteins in cells
• 11:23that are found in the stomach in a in a
• 11:26manner that may promote tumor growth.
• 11:28So how is it that the microbe
• 11:31interfaces with human proteins?
• 11:33How do they alter?
• 11:34How do those interactions alter the
• 11:36proteins behavior in a manner that could
• 11:39promote the development of cancer,
• 11:41so to break it down a bit when
• 11:43when you have an infection,
• 11:45your body's immune system will
• 11:46respond to try to clear the infection
• 11:48and that that generally involves
• 11:50the recruitment of immune cells.
• 11:52And these immune cells will produce
• 11:53a lot of oxidants or free radicals.
• 11:56These are small molecules that
• 11:58are very reactive.
• 11:59They contain a lot of oxygen.
• 12:00They're starved for electrons,
• 12:02so they react very readily with
• 12:04other molecules in your cells,
• 12:05and they can cause damage to cells.
• 12:07Because of this intrinsic
• 12:09chemical reactivity.
• 12:10And one of the major classes of
• 12:13biomolecules that can get damaged by
• 12:15these oxidants or proteins and proteins
• 12:17are super important because they
• 12:19do a lot of chemistry in ourselves.
• 12:21They they generate energy,
• 12:22they help cells grow.
• 12:24They help them divide.
• 12:25They provide structure to cells.
• 12:26They help mediate interactions between cells,
• 12:29and these are all very important processes
• 12:31that if they become dysregulated,
• 12:34so if they're interrupted or inhibited,
• 12:36messed with in some way,
• 12:37they could lead to the development of cancer.
• 12:41And So what we're trying to understand
• 12:43is when you have an infection and
• 12:45all of these oxidants are produced
• 12:48by the immune system,
• 12:49some of those oxidants will damage proteins.
• 12:52And when those proteins get damaged,
• 12:54do they alter some of these processes
• 12:57that could encourage cancer to form?
• 12:59If that's the case in our data points,
• 13:01to indicates that that is.
• 13:04Then can we identify you?
• 13:06Some of these proteins as new
• 13:08diagnostic markers of cancer risk?
• 13:09So if these proteins are getting
• 13:11damaged early on,
• 13:12can we use them as indicators that
• 13:14cancer may be maybe more likely
• 13:16down the line?
• 13:17Yeah, so I was just about to say, I mean,
• 13:19that sounds like just fascinating
• 13:21work and and I'd really like to
• 13:24dig a little deeper into into that.
• 13:26But first we have to take a
• 13:27short break for a medical minute.
• 13:29So please stay tuned to learn more
• 13:32information about research and to
• 13:34detecting cancer causing proteins
• 13:35with my guest doctor Stavroula Hatzios.
• 13:38Funding for Yale Cancer Answers
• 13:41comes from Smilow Cancer Hospital
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• 14:52to Connecticut Public Radio.
• 14:54Welcome back to Yale Cancer Answers.
• 14:57I'm doctor Anees Chagpar and I'm joined
• 14:59tonight by my guest doctor Stavroula Hatzios.
• 15:02We're discussing some of her recent
• 15:04research and right before the break
• 15:06she was starting to tell us about H.
• 15:08Pylori. Now, for those of
• 15:09you who are just joining us,
• 15:11you know each pylori.
• 15:13It's that bacteria that sits in your
• 15:15stomach and that causes ulcers and gastritis.
• 15:18And things like that.
• 15:19And we never really think about it
• 15:22necessarily as being associated with cancer.
• 15:25However, Savula tells us that it's actually
• 15:28a leading cause of gastric cancer and
• 15:31the mechanism for that is something that
• 15:34she and her lab is working on discovering
• 15:38because not everybody who has H.
• 15:40Pylori gets gastric cancer.
• 15:42Thank goodness, but some people do.
• 15:45And so stavroula right before the
• 15:47break you were telling us that one
• 15:49of the potential mechanisms of this,
• 15:51if I understood correctly,
• 15:53is that with this.
• 15:55Infection with this H pylori your
• 15:58immune system starts to kind of
• 16:02act on that infection.
• 16:03It it kind of gets geared up as it
• 16:06would to any infection and starts
• 16:08manipulating some proteins and that those
• 16:11proteins might actually signal cancer.
• 16:13Is that right?
• 16:16Yes, that's what we believe
• 16:17and what we're investigating,
• 16:18and so we think that a lot of the
• 16:21inflammation that occurs during H.
• 16:23Pylori infection, which is accompanied
• 16:26by the production of oxidants.
• 16:28Those small molecules
• 16:29that are highly reactive,
• 16:31leads to changes in your cells, the proteins,
• 16:34the DNA that helps nucleate cancer formation,
• 16:37and as you mentioned,
• 16:39we're focusing on the proteins.
• 16:40How do those change in a way
• 16:42that may promote tumor growth?
• 16:44Our lab is using.
• 16:46Some advanced chemical tools that
• 16:48allow us to identify specific
• 16:51proteins and human gastric cells
• 16:53that get damaged or modified by
• 16:56these oxidants produced during H.
• 16:58Pylori infection,
• 16:59so we can basically canvas the whole
• 17:01cell with these chemical tools and
• 17:03say what proteins are you getting
• 17:06modified by these oxidants and then
• 17:08independently look at these proteins
• 17:10using biochemistry and some biology.
• 17:12Other very interesting
• 17:14tools in our toolkit to ask.
• 17:16What happens when these proteins are
• 17:18modified that may promote tumor growth,
• 17:20and for that we use a number
• 17:22of different model systems,
• 17:24both in the lab and using a number
• 17:26of other different systems to look
• 17:28at tumor growth as a result of
• 17:30these modifications to the proteins,
• 17:32the long term goal here is to
• 17:35identify modified proteins that
• 17:36could be used to diagnose cancer
• 17:38risk much earlier in an infection.
• 17:41So you might imagine,
• 17:42as you mentioned previously,
• 17:43if someone presents at a clinic with an H.
• 17:46Pylori infection,
• 17:46maybe there could be a biopsy taken
• 17:49where we look specifically for
• 17:52proteins that we've identified in the lab.
• 17:55Promote tumor growth and see if
• 17:57those have been changed in a way
• 18:00that aligns with that outcome.
• 18:02And if you can detect those small
• 18:04molecular changes very early in
• 18:06an infection that that may help
• 18:09improve outcomes on the patient side
• 18:11so that that's an interesting theory
• 18:14stavroula, but one of the things
• 18:16that you mentioned before the break,
• 18:18which is true, is that there is
• 18:21this lag time right between when
• 18:23you get an infection when you have.
• 18:25Gastritis and when you may ultimately
• 18:27end up with gastric cancer,
• 18:30are there ways that we can manipulate these
• 18:34proteins or or reduce risk in some way?
• 18:38Once we identify these proteins,
• 18:41right? That is absolutely the goal.
• 18:44So not only could such proteins
• 18:46serve as indicators of cancer risk,
• 18:49but the nice thing about proteins,
• 18:51and particularly a lot of
• 18:52the proteins that we study,
• 18:54is that a lot of them carry enzymatic.
• 18:56Function so there are enzymes.
• 18:57That means that they can perform
• 18:59different chemistry in the cell.
• 19:00They can perform chemical reactions and
• 19:02those are proteins that are really nicely
• 19:05targeted by small molecules by drugs.
• 19:07And thus if if these proteins
• 19:10that are involved in the infection
• 19:12response and down the line,
• 19:15increasing the risk of tumor
• 19:16growth can be targeted by drugs,
• 19:18then you also have the opportunity
• 19:20to develop new chemotherapeutics
• 19:22that could help actually treat
• 19:23cancers that result down the
• 19:25line from these infections.
• 19:27So not only are the proteins
• 19:29important as diagnostic indicators,
• 19:30but also carry the potential to
• 19:32be new drug targets for actually
• 19:34treating the cancer itself.
• 19:36Wouldn't it be better if we were
• 19:38able to somehow manipulate these
• 19:40proteins to prevent cancer?
• 19:42Is that something that's
• 19:43being looked at? Yes, I think
• 19:45we're not quite there yet.
• 19:47We're still at the early stages
• 19:49of trying to identify what these
• 19:51proteins are and how they relate
• 19:53to the time course of cancer
• 19:54to the progression to cancer.
• 19:56From the point of infection.
• 19:58But yes, I think that there's
• 20:00very much a possibility to
• 20:01intervene at a very early stage.
• 20:03If you do sort of a screen for such
• 20:07proteins at early points of infection,
• 20:09perhaps in in an ideal scenario.
• 20:12In a case of a childhood infection,
• 20:14for example,
• 20:14and if you see this sort of indication,
• 20:17then intervene at that point
• 20:18with these drugs that I mentioned
• 20:20might be down the line to kind
• 20:22of inhibit the activity that
• 20:23could lead to tumor development.
• 20:25You know you mentioned that
• 20:27half the world's population.
• 20:28Actually carry this Helicobacter pylori in
• 20:31our stomachs and for the majority of us.
• 20:33Thank goodness we never have any problems.
• 20:36There's a subset that get ulcers
• 20:39and a subset even smaller that
• 20:41that goes on to get cancer.
• 20:44And I wonder whether.
• 20:47The latter subset who get cancer is
• 20:51a subset who actually get ulcers
• 20:55versus they can get cancer without
• 20:59having that intervening gastritis,
• 21:01inflammation, kind of phase.
• 21:03In other words,
• 21:05if I have an asymptomatic infection with H.
• 21:10Pylori and I just carry this,
• 21:12but it never really bothers me.
• 21:14Am I at the same risk of
• 21:16getting gastric cancer?
• 21:17As a result of carrying that bug,
• 21:20as I would be if I not only carried H.
• 21:23Pylori but that H.
• 21:25Pylori went on to give me gastritis
• 21:27and ulcers and so on and so forth.
• 21:29And then I get gastric cancer.
• 21:32Do you understand my question?
• 21:34Yeah, I think so.
• 21:35And I should note again that I'm not
• 21:37a clinician, so this is certainly
• 21:39not my my area of expertise.
• 21:41But I will say my understanding
• 21:43is that the latter holds true,
• 21:44so those individuals who do develop ulcers.
• 21:47You know, chronic inflammation.
• 21:49Gastritis are the subset that are at
• 21:51greater risk for developing cancer
• 21:53down the line and the the model in
• 21:55the field is that each pylori induces
• 21:58infection in some host induces this
• 22:00chronic inflammation and in some
• 22:03hosts and some humans who have the.
• 22:05The microbe overtime that leads to
• 22:07the development of this inflammation
• 22:08in the tissue and that process is
• 22:10what seeds the development of the
• 22:12cancer decades down the line as well.
• 22:14So it does correlate strongly
• 22:16with the incidence of inflammation
• 22:18and people who have each pylori
• 22:20and that makes so much sense because
• 22:22we've seen that in other cancers as well,
• 22:24where it really is. This inflammation,
• 22:27the damage to the tissues.
• 22:29This idea that you get inflammation?
• 22:32You get fibrosis.
• 22:34You get free radicals.
• 22:36You you get, you know, an area of
• 22:41tissue which is not as well perfused.
• 22:46That can lead then to
• 22:49cancers and and so you know,
• 22:52presumably the tests that you're
• 22:54developing to look at these these
• 22:57infections might be something that
• 22:59very easily could be done at the time
• 23:02that somebody presents for a biopsy.
• 23:05Diagnosing the H.
• 23:06Pylori to begin with when they
• 23:08they have symptoms of gastritis.
• 23:11The next question is,
• 23:13you know if we know that it is the
• 23:16case that you know these gastric
• 23:19cancers tend to emerge in an area
• 23:21of inflammation and we we can kind
• 23:24of see in your research and that
• 23:26of others that the the pathway
• 23:29seems to be these free radicals.
• 23:31These small molecules and and damage to
• 23:35proteins and an inflammatory response,
• 23:38and so on and so forth.
• 23:40With your chemical toolbox where you're
• 23:43looking at these altered proteins.
• 23:46Have you looked at that in
• 23:48other cancers as well,
• 23:50and isn't necessarily the case that
• 23:53these are always related to microbes?
• 23:57Or is it possible that some inflammation
• 24:00may be due to other causes,
• 24:03but that the end pathway,
• 24:05the end result in terms of the small
• 24:07molecules and the tissue damage
• 24:09and the protein damage, et cetera?
• 24:11With the inflammatory response is the same?
• 24:16That's a great observation.
• 24:17And yes, I think it is very likely to
• 24:20be the case that a lot of these same
• 24:22protein damage pathways are are shared
• 24:25or are common amongst other cancers.
• 24:27We specifically, my lab specifically
• 24:29has not looked at other non
• 24:32infection associated cancers,
• 24:33but other labs have begun looking
• 24:36at this question and have certainly
• 24:38done it in other contexts as well,
• 24:41and I think that there will be an emerging
• 24:44picture of some proteins that get damaged.
• 24:47By inflammation and oxidative stress
• 24:49and variety of contexts and that these
• 24:53may provide very important clues
• 24:55for the risk of cancer development,
• 24:58and I should also mention that one thing
• 25:00that we haven't touched on is DNA damage,
• 25:03which is perhaps the more well
• 25:04known target of these oxidants that
• 25:06are generated during inflammation.
• 25:08And that's something that is certainly
• 25:10very common across many different types
• 25:13of cancers resulting from infection or not.
• 25:15Oxidants can damage DNA.
• 25:17Directly,
• 25:18and that can lead to mutations and
• 25:20instability of the genome that ultimately
• 25:22helps seed cancer formation as well.
• 25:26Yeah, the the problem with that though,
• 25:28is that as you mentioned,
• 25:30the nice thing about proteins is that
• 25:32potentially you can do something about it.
• 25:33So are people looking at, you know,
• 25:36trying to figure out how you can
• 25:38manipulate the system so that.
• 25:42You can kind of counteract DNA damage.
• 25:44My perception is that that's
• 25:45a little bit more difficult.
• 25:48I think you're right. Yeah, I'm not.
• 25:50I'm not familiar with specific work in
• 25:52that area, and I think it's it's a very
• 25:55important point that the benefit the
• 25:57advantage to looking at proteins, which
• 25:59is still a very emerging area of research,
• 26:02is that you have the opportunity to
• 26:04intervene and actually do something about it.
• 26:06And they also have the added advantage
• 26:09of being both diagnostic indicators
• 26:11or providing some some clues.
• 26:14What might be to come down the line,
• 26:15but also an opportunity to
• 26:18intervene through drugs?
• 26:19Small molecule approaches to
• 26:21help alter these outcomes?
• 26:22So I think for us,
• 26:23that's why there's such an
• 26:25exciting area of research,
• 26:26particularly as they relate to microbes.
• 26:29Yeah, you know, as you were talking about
• 26:31kind of these pathways and the way that H.
• 26:34Pylori works in terms of
• 26:37gastric cancer by you know,
• 26:39kind of getting the immune system to
• 26:42respond to it and then creating these.
• 26:45Small molecules and inflammation and so on.
• 26:49It. It made me think about other
• 26:51infections that we know also cause cancer,
• 26:54but that are not bacterial so we know H.
• 26:57Pylori is a is a little bacterium
• 26:59that lives in our stomachs.
• 27:01But we also know that many other
• 27:04cancers are caused by viruses.
• 27:06So thinking about hepatitis, for example,
• 27:10the pathway seems to be very similar
• 27:12in terms of you know, creating.
• 27:14Inflammation and fibrosis and free
• 27:17radicals and so on and so forth.
• 27:20Is there a difference in terms
• 27:23of how bacteria and viruses work
• 27:26in terms of developing cancer?
• 27:28And is it possible for your
• 27:31research to potentially look at
• 27:33virally mediated cancers as well?
• 27:37Sure, I think that there are opportunities
• 27:39to apply similar approaches to viral
• 27:42infections that are associated with cancer.
• 27:45And of course a lot of viruses have been
• 27:48connected to very important malignancies,
• 27:51HPV, human papilloma virus,
• 27:53and cervical cancer.
• 27:54That's perhaps one of the
• 27:56most well known connections,
• 27:58but there are several others,
• 27:59like hepatitis C, Epstein Barr virus,
• 28:02and the link between viruses and
• 28:04cancer has been explored for
• 28:07quite a long time and a lot more is
• 28:10known about how viruses can engage with
• 28:13the human cell to to cause cancer.
• 28:17So some of the pathways may be similar,
• 28:19but we think that they may also be
• 28:21very distinct with regards to microbes,
• 28:22but at the same time,
• 28:23these approaches I think will be
• 28:25very valuable for assessing viral
• 28:27infections and finding common pathways.
• 28:29Doctor Stavroula Hatzios is an
• 28:31assistant professor of molecular,
• 28:33cellular and developmental biology and of
• 28:35chemistry at the Yale School of Medicine.
• 28:38If you have questions,
• 28:40the address is canceranswers@yale.edu
• 28:42and past editions of the program
• 28:45are available in audio and written
• 28:48form at yalecancercenter.org.
• 28:48We hope you'll join us next week to
• 28:51learn more about the fight against
• 28:53cancer here on Connecticut Public Radio.
• 28:55Funding for Yale Cancer Answers
• 28:57is provided by Smilow Cancer Hospital.