Melanoma Awareness Month 2020

Transcript

00:00 --> 00:03Support for Yale Cancer Answers comes from AstraZeneca,
00:03 --> 00:14the Beyond Pink campaign aims to empower metastatic breast cancer patients and their loved ones to learn more about their diagnosis and make informed decisions.
00:14 --> 00:17Learn more at lifebeyondpink.com.
00:17 --> 00:20Welcome to Yale Cancer Answers with your host
00:20 --> 00:21Doctor Anees Chagpar.
00:21 --> 00:31Yale Cancer Answers features the latest information on cancer care by welcoming oncologists and specialists who are on the forefront of the battle to fight cancer. This week
00:31 --> 00:36it's a conversation about Melanoma research with doctor Jeffrey Ishizuka.
00:36 --> 00:41Doctor Ishizuka is an Assistant Professor of Medical Oncology at Yale School of Medicine,
00:41 --> 00:45where Doctor Chagpar is a Professor of Surgical Oncology.
00:45 --> 00:51Jeff, maybe we could start off by you telling us a little bit about yourself and what you do.
00:51 --> 00:59I'm a physician-scientist and that means that I spend part of my time treating cancer patients and part of my time in the lab looking
00:59 --> 01:02for new treatments for those patients.
01:02 --> 01:09And so tell us a little bit more about the kinds of patients that you treat and the kinds of research that you do.
01:09 --> 01:12I see Melanoma patients and I'm an immunologist
01:12 --> 01:15by training. And that means I study ways to
01:15 --> 01:19make the patient's immune system work better,
01:19 --> 01:22to attack the cancer.
01:22 --> 01:26Tell us more about that, we've talked on the show a little bit about immunotherapy and so on,
01:26 --> 01:31but tell us a little bit more about the broad spectrum of immunotherapy.
01:31 --> 01:35How exactly does it work and then the role that it plays in Melanoma.
01:35 --> 01:38There are a couple of types of immunotherapy.
01:38 --> 01:43And for a long time we knew that the immune system had the potential to control cancer,
01:43 --> 01:46but I'd say the two big advances that are more recent are on the one hand,
01:46 --> 01:54CAR T cells. And those are cells that are taken out of the patients body and reprogrammed to go back in and attack the tumor, and immune checkpoint
01:54 --> 01:58blockade. And these are drugs that cut the brakes on the immune system.
01:58 --> 02:02Those brakes stop the immune system from attacking the cancer.
02:02 --> 02:03And when you get rid of them,
02:03 --> 02:08the cancer is vulnerable to immune attack.
02:08 --> 02:12Tell us about which of these you work on, and
02:12 --> 02:15how exactly they work in Melanoma.
02:15 --> 02:22In Melanoma, immune checkpoint blockade has really been one of the biggest developments
02:22 --> 02:26really in the last, well maybe ever in the disease.
02:26 --> 02:31And I think Melanoma was the first disease where
02:31 --> 02:37these drugs were developed and remains one of the ones where they work the best.
02:38 --> 02:41Can you talk about this immune checkpoint blockade.
02:41 --> 02:45Is there more than one molecule that needs to be blocked?
02:45 --> 02:49How does that work? Why does the immune system have brakes to begin with?
02:49 --> 02:54These are great questions and they're really at the forefront of the field right now,
02:54 --> 02:58so there are certainly at least a few molecules that are important.
02:58 --> 03:02And all of the ones we learned about first are on the surface of T cells,
03:02 --> 03:07which we know are one of the important cells for controlling cancer.
03:07 --> 03:09There are a number of molecules that target
03:09 --> 03:13PD-L1 and that's a major inhibitory pathway in the T cells,
03:13 --> 03:15and also molecules that target CTL A4,
03:15 --> 03:18which is another inhibitory pathway in T cells.
03:18 --> 03:25And what we learned is when you block either one of these and sometimes if you block them both together it works even better.
03:25 --> 03:28The T cells can get supercharged to attack the cancer.
03:28 --> 03:30Why is it that
03:30 --> 03:32they have breaks to begin with?
03:32 --> 03:38The immune system is supposed to be able to identify foreign stuff in our bodies and get rid of it.
03:38 --> 03:41So why doesn't that work in cancer?
03:41 --> 03:45Why is it that we need to take off these brakes?
03:45 --> 03:47Why do they have breaks to begin with?
03:47 --> 03:51This is the foundational question of immunology,
03:51 --> 03:54the distinction between self and nonself.
03:54 --> 03:59All cells need to be able to get rid of foreign things just as you said,
03:59 --> 04:00but at the same time
04:00 --> 04:09they need to have mechanisms to avoid attacking the normal cells in the body that are healthy and so
04:09 --> 04:15why is it that the immune system thinks that these cancer cells are normal?
04:15 --> 04:26I think it's really because cancer cells arise from normal cells as normal cells become dysregulated as they acquire genetic errors called mutations.
04:26 --> 04:29And eventually you develop cancer.
04:29 --> 04:33And because the cancer cell arises from a backdrop of normal cells,
04:33 --> 04:40doing normal cell things, the immune system has to find specific signals of damage or mutations that
04:40 --> 04:43look abnormal in order to recognize cancer.
04:43 --> 04:46So you're telling me that normally it won't do that?
04:48 --> 04:54Some tumors are recognized by the immune system and the immune system can actually get rid of them,
04:54 --> 05:02and other aren't. And really what we're trying to understand and at the heart of the field is how can we take tumors that are not well recognized by
05:02 --> 05:07the immune system and turn them into tumors that the immune system can see and destroy?
05:07 --> 05:10And so it seems to me that if you take that problem just at its face,
05:10 --> 05:13there are two ways of doing that.
05:13 --> 05:18One is to make the tumor look more abnormal so that the immune system
05:18 --> 05:27realizes, I need to attack it and get rid of it without actually revving up the immune system or getting rid of the
05:27 --> 05:36brakes and the other is to supercharge the immune system as you put it to make it more sensitive to recognizing what might be abnormal.
05:36 --> 05:41Yeah, that's right, and I think people are working at both sides of that problem.
05:41 --> 05:49We and others in the lab, are thinking of strategies both to make tumors put out signs for the immune system, saying,
05:49 --> 05:55come get me and also looking for new ways to charge the immune system to be more aggressive against cancer.
05:55 --> 05:57Tell us more about the first,
05:57 --> 06:04because I think that we've heard a little bit about checkpoint inhibitors,
06:04 --> 06:11but we really haven't heard a lot about the work that's going on to have tumor cells put out those signs that
06:11 --> 06:22say, come get me. And it seems to me that might be a way to allow the immune system without getting supercharged to eat up or
06:22 --> 06:24get rid of these cancer cells,
06:24 --> 06:26because one of the problems,
06:26 --> 06:35as you point out, of having a supercharged immune system is that it can then attack its own cells.
06:35 --> 06:37Yeah, that's a great point and
06:37 --> 06:42we've been thinking, and others as well,
06:42 --> 06:49that it comes down to tricking the tumor cell into making inflammatory signals,
06:49 --> 06:56tricking it into making kind of an antiviral response that recruits anti tumor immune cells into the micro environment,
06:56 --> 06:57and I think
06:57 --> 07:06you can go about that by infecting the tumor with a virus or making it think it's infected with a virus or triggering certain danger signals in the micro environment
07:06 --> 07:10directly around the tumor.
07:10 --> 07:15Tell us more about that work, is that actually something that's being done?
07:15 --> 07:19Is it in clinical practice?
07:19 --> 07:20How do we do that?
07:20 --> 07:29There are a number of clinical trials now using stimulators of viral pathways that look like DNA or RNA,
07:29 --> 07:36things that viruses make and that ourselves have dedicated sensors in order to detect,
07:36 --> 07:42and I think none of them has proven to be the Magic bullet for cancer yet.
07:42 --> 07:46But there are still some technical hurdles to workout.
07:46 --> 07:49And I think we're getting there though.
07:49 --> 07:56Why has that not proven to be as successful as supercharging the immune system?
07:56 --> 08:03I think one of the challenges is that cancer in many cases can spread to many locations,
08:03 --> 08:09and when you think about triggering an inflammatory response in the tumor bed,
08:09 --> 08:12you're really thinking about triggering it,
08:12 --> 08:14not just at one site,
08:14 --> 08:16but at many sites all at once,
08:16 --> 08:18and so finding ways to send drugs
08:18 --> 08:26to all of the different sites that cancer occupies in the body is one of the major challenges to getting this approach to work.
08:26 --> 08:33The other approach then is the one that is the mainstay of immunotherapy,
08:33 --> 08:38which is to quote supercharge the immune system to get rid of the blocks.
08:38 --> 08:43I always think of it like Harry Potters invisibility cloak,
08:43 --> 08:48right. The tumor has kind of made itself invisible to the immune system,
08:48 --> 08:57and it's getting rid of that that cloak and getting the immune system to recognize it and to go after it and two,
08:57 --> 08:59to be quote supercharged now.
08:59 --> 09:09You mentioned two molecules, in particular CTL A4 and PDL1, tell us a little bit about the differences between the two.
09:09 --> 09:14I mean we have drugs that will block either pathway.
09:14 --> 09:17How do you figure out which one to use?
09:17 --> 09:20Tell us more about that interplay.
09:20 --> 09:29I think we still don't fully understand the mechanism of either drug and either pathway.
09:29 --> 09:32And people have done a lot of good work,
09:32 --> 09:36in fact, the Nobel Prize was awarded a few years back for some of that work,
09:36 --> 09:39but I wouldn't say that we completely understand which,
09:39 --> 09:41even sometimes which cells are being targeted,
09:41 --> 09:44but certainly which pathways within the cell are being activated.
09:44 --> 09:47So a lot of how we figured this out has been empirically.
09:47 --> 09:52We've done clinical trials with different drugs or different combinations of drugs,
09:52 --> 09:55and we've seen what's been effective for patients,
09:55 --> 09:59and the hope is going forward that as we learn more about the immune system,
09:59 --> 10:04and as we learn more about the tumor that we will be able to do better
10:04 --> 10:09and even predict the next set of these drugs that could be usefully combined.
10:09 --> 10:14So tell us more about the differences between CTLA for an PDL1.
10:14 --> 10:24I get the fact that we've discovered these kind of fortuitously and empirically and have just made drugs that affect each of these pathways,
10:24 --> 10:26and seeing that they work.
10:26 --> 10:29But we must know more about these actual molecules.
10:29 --> 10:33Yeah, they both play an inhibitory role in T cells.
10:33 --> 10:37I think it's broadly thought
10:37 --> 10:42that one of them plays more of a role in T cells initially getting primed against the tumor,
10:42 --> 10:52but maybe plays more of a role in lymph nodes then generating the T cells that are capable of responding whereas the other one,
10:52 --> 11:01that speedy one may play more of a role in activating the T cells that are already primed against the tumor that already have the capacity to attack the tumor.
11:01 --> 11:08And I'm going to steer clear of the term of exhaustion because there are a lot of debates about whether T cells
11:08 --> 11:10are actually exhausted or not,
11:10 --> 11:20but there's this idea that T cells can, after seeing a lot of tumor antigen stop responding very well that they can become dysfunctional and so one
11:20 --> 11:23of the things that PDL1 blockade does,
11:27 --> 11:31is to make the T cells that have become dysfunctional more functional.
11:31 --> 11:35And so if these two pathways then are complementary,
11:35 --> 11:42one being more so for priming T cells and one being more so for T cells that are already primed,
11:42 --> 11:53has there been any work looking into either concurrent therapy or sequential therapy of different immuno therapies that might work better than either in isolation?
11:53 --> 11:56There has, and in Melanoma combining two drugs,
11:56 --> 11:58one that targets CTL A4.
11:58 --> 12:07and one that targets PDL1 seems to be better than using either drug alone and potentially better than using them both in sequence,
12:07 --> 12:17although the latter is a less clear conclusion.
12:17 --> 12:27And one of the exciting things in this field has been seeing the slew of approvals for immuno therapies in different cancer types in Melanoma.
12:27 --> 12:39Certainly it's become standard of care in the frontline for most patients and it's being explored in basically every stage of care of the disease other than for disease that
12:39 --> 12:45can just be removed and surgically cut out in the early stages and really beyond Melanoma,
12:45 --> 12:53it spread throughout many many solid tumor types and it's being tried in almost any tumor type you can think of.
12:53 --> 13:00And so two questions. First question is one of the things you mentioned earlier as being one of the
13:00 --> 13:08downfalls of some therapies is that it can't always get to all of the cells where the tumors may be hiding.
13:08 --> 13:16Does immunotherapy have that problem in terms of getting to the T cells and activating them or supercharging them?
13:16 --> 13:21Or is that concept, this may not work if there's a tumor,
13:21 --> 13:23for example in the brain?
13:23 --> 13:27Because this drug can't cross the blood brain barrier?
13:27 --> 13:31Or does it affect T cells wherever they are?
13:31 --> 13:38We know that we can get effects certainly in the brain.
13:38 --> 13:51So you can see effects of these drugs in what are thought of usually as sites of the body that are hard to get to or immune privilege sites but
13:51 --> 13:53I guess what I don't know for sure,
13:53 --> 13:58it's hard to say is whether there is a problem activating immune cells somewhere in the body.
13:58 --> 14:07That is to say, whether we're getting these drugs as effectively as possible to all the immune cells that might be able to be mobilize against the tumor.
14:07 --> 14:14We're going to learn a lot more about Melanoma immunotherapy right after we take a short break for a medical minute.
14:14 --> 14:22Please stay tuned to learn more about this research with my guest doctor Jeffrey Ishizuka. Support for Yale Cancer Answers comes from AstraZeneca.
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15:22 --> 15:26You're listening to Connecticut public radio.
15:26 --> 15:29Welcome back to Yale Cancer Answers.
15:29 --> 15:35This is doctor Anees Chagpar andnI'm joined tonight by my guest doctor Jeffrey Ishizuka.
15:35 --> 15:41We're talking about Melanoma research and in particular we're talking about immunotherapy.
15:41 --> 15:47Jeff, right before the break we were talking a little bit about immunotherapy in terms of,
15:47 --> 15:51really getting the immune system to attack cancer cells,
15:51 --> 15:55which it may not recognize because as you put it,
15:55 --> 15:58these cancer cells come from normal cells and that
15:58 --> 16:07may not be as foreign looking to the immune system to really trigger it and we talked a little bit about two separate pathways,
16:07 --> 16:11CTL A4 and PDL1 and the fact that we now have drugs,
16:11 --> 16:20this explosion of drugs in immunotherapy targeting these two pathways and how this really has become the mainstay of therapy,
16:20 --> 16:23particularly for cancers like Melanoma.
16:23 --> 16:27I had a few questions to kind of follow up on that.
16:27 --> 16:32The first is, tell us a little bit about the side effects.
16:32 --> 16:35We think about
16:35 --> 16:39chemotherapy, and you know, traditionally,
16:39 --> 16:47chemotherapy was therapy that kills off cancer cells and was really thought to be therapy that switches off
16:47 --> 16:55rapidly dividing cells and so people ended up losing hair and maybe getting sick because it effects your GI lining,
16:55 --> 16:57which are rapidly turning over cells.
16:57 --> 17:01Do you get the same kind of thing in immunotherapy,
17:01 --> 17:05or are there other side effects that are the results of
17:05 --> 17:11kind of supercharging this immune system and getting the immune system to attack healthy cells?
17:11 --> 17:13So I think that's it exactly.
17:13 --> 17:20Many of the side effects that you get from immunotherapy are actually side effects of supercharging the immune system,
17:20 --> 17:24so the immune system can accidentally attack different areas of the body.
17:24 --> 17:27Some of the things we see are inflammation in the lungs,
17:27 --> 17:31inflammation in the GI system we see inflammation of the endocrine system,
17:31 --> 17:34and when we first started seeing these side effects,
17:34 --> 17:37there wasn't a good sense of how you treat them,
17:37 --> 17:39how you manage them, or even how you monitor.
17:39 --> 17:41We didn't really know what to look for.
17:41 --> 17:45But I will say that as experience with these agents has progressed,
17:45 --> 17:49we've gotten better at detecting these side effects as they occur,
17:49 --> 17:56and managing them, usually using immunosuppressives and one of the questions that comes up when you start saying,
17:56 --> 18:02well, you're using drugs to charge the immune system and at the same time to shut down the immune system,
18:02 --> 18:05is that going to be is going to be bad for the patients.
18:05 --> 18:11Are they going to have that outcomes and the data isn't really completely mature on this yet,
18:11 --> 18:14but it certainly appears from the early data that
18:14 --> 18:22you can safely give these immunosuppressives and that you don't at least don't clearly make their responses against the cancer
18:22 --> 18:26worse.
18:26 --> 18:32That's really interesting. Why would that be the case? I can imagine that when we think about people who are immunosuppressed,
18:32 --> 18:37people who for example have HIV or other things that turn off their immune system,
18:37 --> 18:40they are more at risk of developing cancer,
18:40 --> 18:45and I guess for the same reason that you talked about before the break,
18:45 --> 18:47which is your immune system,
18:47 --> 18:55unbeknownst to you, might be getting rid of little cancers that you don't know you have because it recognizes them and it gets rid of them,
18:55 --> 19:01and so if you are immuno compromised you're at increased risk of getting cancer,
19:01 --> 19:04and that's the whole point of
19:04 --> 19:10supercharging the immune system to get rid of these cancers.
19:10 --> 19:21Why is it that giving people an immunosuppresant at the same time as an immuno supercharger doesn't seem to affect the cancer in a bad way?
19:21 --> 19:25A couple of potential thoughts here.
19:25 --> 19:32The first one is that I want to be careful we don't know for sure that it doesn't affect the
19:32 --> 19:34response to therapy in a negative way.
19:34 --> 19:37I think what we can say is that
19:37 --> 19:44at first blush, patients who needed immunosuppressives because they had these bad immune effects and got them didn't do obviously worse,
19:44 --> 19:46at least in the early studies
19:46 --> 19:55then patients who didn't need them in the first place and that actually could be a kind of selection bias issue where the patients who needed the immunosuppressives
19:55 --> 19:58actually were having the strongest immune responses to begin with,
19:58 --> 20:08and so I think we have to do some careful experiments in a controlled setting to see whether it was really true that the immunosuppressives weren't having any effect there.
20:08 --> 20:14And I think that's probably the main thing that I would think about for that issue.
20:14 --> 20:20The other question that I have is, these autoimmune side effects,
20:20 --> 20:26the side effects of people's immune system now attacking their own normal cells,
20:26 --> 20:28are those permanent? Are
20:28 --> 20:37they forever or are they short lived? I mean when you get chemotherapy and you lose your hair,
20:37 --> 20:39your hair will grow back.
20:39 --> 20:44Is it the same with immunotherapy that this is a short term thing?
20:44 --> 20:47Or when your immune system attacks your lungs,
20:47 --> 20:50now you've got pulmonary fibrosis forever?
20:50 --> 20:55I think it depends on the type of immune side effect that we're talking about.
20:55 --> 20:57I think many of them,
20:57 --> 20:59if they're controlled with immunosuppressives,
20:59 --> 21:04and if you take the patient off of the immunotherapy, will actually go away.
21:04 --> 21:06So we see this in a lot of cases,
21:06 --> 21:09inflammation in the colon, or inflammation in the lungs.
21:09 --> 21:16I think the case in which this isn't necessarily true is when the immune system attacks the cell type
21:16 --> 21:26that produces hormones in the body and destroys all of that cell type because in that case you may not really know what's going on until the cell type
21:26 --> 21:30is gone, and after that there's really no bringing it back.
21:30 --> 21:37So in most cases we actually have been able to give hormone replacement.
21:37 --> 21:40It's extremely bad if it's not detected,
21:40 --> 21:45but in a lot of cases it can be solved by giving a pill a day.
21:45 --> 21:47When you talk about hormones,
21:47 --> 21:54are you talking about thyroid are you talking about ovaries, what hormones are we talking about?
21:54 --> 21:57Yeah, so thyroid is one that you certainly see,
21:57 --> 22:05but you see actually a number of other hormones that are produced in the brain that can also be altered,
22:05 --> 22:07and these can be be more rare,
22:07 --> 22:10but can be pretty dramatic if you see them.
22:10 --> 22:14So given the side effects of immunotherapy,
22:14 --> 22:17is immunotherapy really better than classic chemotherapy?
22:17 --> 22:24You had mentioned that immunotherapy has now become standard of care for Melanoma.
22:24 --> 22:26Is it better than what we used to do?
22:28 --> 22:31We used to give chemotherapy for Melanoma,
22:31 --> 22:32right?
22:32 --> 22:36And Melanoma is not particularly responsive to chemotherapy,
22:36 --> 22:41and I think what excited everyone in the field and it's given us all
22:41 --> 22:44a lot of excitement and a lot of hope is not even that
22:44 --> 22:48everyone responds to these immunotherapy's because they don't,
22:48 --> 22:52not enough patients do, and that's something we don't really understand.
22:52 --> 22:54We're trying to understand it in the lab,
22:54 --> 22:59but it's that some of the patients who respond seem to just keep responding,
22:59 --> 23:07and some of them respond so well and for so long that we've actually started to believe that we can take the patients off of the drugs,
23:07 --> 23:10the immunotherapy drugs, and that the cancer won't return.
23:10 --> 23:15And this is true even in some cases for very aggressive disease.
23:15 --> 23:19And so seeing those effects are the ones that have really made everybody excited.
23:19 --> 23:26And you see that in clinical trials when we study how patients survive on different drugs and
23:26 --> 23:30it was no contest between the immunotherapy's and chemotherapy.
23:30 --> 23:44When we talk about therapy for cancer a lot of times we're talking about personalized medicine and we're talking about how we can figure out what a cancer likes to
23:44 --> 23:48eat, what receptors cancer has,
23:48 --> 23:51what genes are turned on and turned off,
23:51 --> 23:54and then we target our therapy accordingly.
23:54 --> 24:04Talk about immunotherapy. It seems to me like we're talking about a blanket turning on supercharging the immune system,
24:04 --> 24:09is that right, or are there ways where we're actually tailoring this therapy?
24:09 --> 24:20Are we looking at who those people are that are super responsive to immunotherapy versus the people who are not super responsive to immunotherapy?
24:20 --> 24:25And which immunotherapy might work better in particular patients?
24:25 --> 24:28Yeah, so this question is near and dear to my heart.
24:28 --> 24:39We in general don't do a great job of selecting patients to get particular immunotherapy, there is one biomarker which is the expression of PDL1 in the tumor as
24:39 --> 24:43we talked about PDL1 and PD1 is one of these key pathways,
24:43 --> 24:51so if you have PDL1 expressed in the tumor microenvironment either by immune cells in the micro environment or by the tumor,
24:51 --> 24:57we know that you are more likely to have a response to targeting the PD1 PDL1 axis.
24:57 --> 25:07But basically everyone in the field spends a lot of time complaining about this biomarker because we know there are a lot of patients who will have PDL1 expression
25:07 --> 25:10in their tumor who won't respond well to these drugs.
25:10 --> 25:18And conversely, there are a lot of patients who won't have PDL1 expression in the tumor who will still respond to these drugs.
25:18 --> 25:20So what's the point of the biomarker then?
25:20 --> 25:28We know it's better than not using it in terms of you have some predictive value and in some cases you might not even be able to see
25:28 --> 25:32a signal of the drug working in a patient population and unless,
25:32 --> 25:37you used a biomarker, and also it's a stand in because we haven't done a good enough job yet of
25:37 --> 25:40finding better ones.
25:40 --> 25:44So we have this biomarker that if you have it,
25:44 --> 25:49you won't necessarily respond to the immunotherapy, if you don't have it,
25:49 --> 25:52you may still respond to the therapy,
25:52 --> 25:57so either way you're likely going to get immunotherapy if you have Melanoma,
25:57 --> 26:01regardless of whether you have the biomarker or not.
26:01 --> 26:06That's true, and that's where I think we have the potential to do much better,
26:06 --> 26:10particularly as we talked about these two pathways,
26:10 --> 26:19there are a lot of other immuno regulatory pathways that can activate immune cells or can activate the tumor to recruit immune cells.
26:19 --> 26:23And we're still at the beginning of understanding these.
26:23 --> 26:31But as these drugs come out and as they are available we have the potential to start thinking about OK for a given patient.
26:31 --> 26:37How can we assess that patients immune system and how can we understand the tumor,
26:37 --> 26:45the genomics, the genetics of the tumor in such a way that we can find the best combination of drugs to work for that patient.
26:45 --> 26:48That sounds really interesting,
26:48 --> 26:59because that sounds like the stuff that we've been doing for awhile now in terms of cancer and looking at cancers in figuring out which therapy is going to work
26:59 --> 27:02better. What targeted pathways are turned on versus turned off.
27:02 --> 27:09Should you be using, you know an anti HER-2 agent in somebody who's got a HER-2-positive breast cancer?
27:09 --> 27:12Or should you be targeting KRAS in lung cancer?
27:12 --> 27:16Sounds like you're moving in the same direction in Melanoma.
27:16 --> 27:19But looking at it from an immune perspective,
27:19 --> 27:23and I should say this is mostly on the research side,
27:23 --> 27:29right now we're trying to understand the flavors of inflammation in the tumor microenvironment.
27:29 --> 27:35The composition of the immune cells that are there and why they're there,
27:35 --> 27:44and then once we understand that, we're simultaneously starting to look at OK if we take pieces of the tumor and study them in tissue culture,
27:44 --> 27:46if we study them in a dish and treat them
27:46 --> 27:52with different immunotherapy drugs, can we see patterns of response from some patients but not from others?
27:52 --> 27:55Those are things that we're working on here,
27:55 --> 28:01and others are working on as well that we think could lead to the development of better biomarkers.
28:01 --> 28:03That's one kind of major approach.
28:03 --> 28:09Another one is focusing on the technologies that have emerged to sequence patient genomes.
28:09 --> 28:11The immune cells from patient genomes.
28:11 --> 28:15We do technologies now to look at individual cells in sequence.
28:15 --> 28:17Everything that that cell is expressing.
28:17 --> 28:24Basically everything it's doing and we can do that for a bunch of cells in the micro environment all at once,
28:24 --> 28:33and the thought is that we may find particular genetic lesions in the tumor that lead to a better response to immunotherapy A versus B.
28:33 --> 28:40We may find particular features of the immune system that interact with the tumor as well that predict that,
28:40 --> 28:47and so I think that in the next 5 or 10 years we're likely to see progress in this direction.
28:47 --> 28:50Whether that will translate affectively into
28:50 --> 28:53guiding precise therapy choice for a patients
28:53 --> 28:59Melanoma, I'm not sure.
28:59 --> 29:01When you talk about,
29:01 --> 29:09essentially taking tumors and looking at the micro environment and seeing the composition of these cancer cells,
29:09 --> 29:13and what kinds of immune therapy they may benefit from,
29:13 --> 29:16you can also look at the immune system and see,
29:16 --> 29:23maybe my immune system is different from your immune system in terms of attacking a particular cell.
29:23 --> 29:26Is that on the right track?
29:26 --> 29:28It's exactly on the right track,
29:28 --> 29:36and you know, even taking a step back when we first started to see that these therapies could work for patients,
29:36 --> 29:38people started to ask,
29:38 --> 29:41why do they work for some patients but not for others?
29:41 --> 29:51And we started to look inside patient tumors and one of the things that was clear is that some patients have a lot of attacking immune cells
29:51 --> 29:54even prior to immunotherapy and others don't.
29:54 --> 29:56And just unpacking that basic
29:56 --> 30:00observation is something we're still doing,
30:00 --> 30:09but as I was mentioning, as we start to understand it as we start to understand the chemical signals that the tumor in the immune system makes.
30:09 --> 30:15It's giving us a lot of inputs to try to determine which drugs could be affective in each case,
30:15 --> 30:18and what the basic flavors of immune micro environment are.
30:18 --> 30:25Doctor Jeffrey Ishizuka is an Assistant Professor of Medical Oncology at the Yale School of Medicine.
30:25 --> 30:35If you have questions, the address is canceranswers@yale.edu and past editions of the program are available in audio and written form at Yalecancercenter.org.
30:35 --> 30:39We hope you'll join us next week to learn more about the fight against cancer
30:39 --> 30:43here on Connecticut Public Radio.

Information

Melanoma Awareness Month 2020 with guest Dr. Ishizuka May 10, 2020 Yale Cancer Center visit: http://www.yalecancercenter.org email: canceranswers@yale.edu call: 203-785-4095