Hope Forward
Hope Forward, a podcast by Rexanna’s Foundation, features real patient stories, expert medical conversations, educational insights, and research updates — bringing together patients, physicians, and advocates united in the fight against lung cancer. Each episode explores real experiences, emerging research, and the work happening every day to shape the future of care.
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Hope Forward
Dr. Don Gibbons on Lung Cancer Breakthroughs: KRAS, Immunotherapy, and Patient Advocacy
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#005 In this episode of the Hope Forward Podcast, Lisa Spain sits down with Dr. Don Gibbons to discuss the latest breakthroughs in lung cancer research, including KRAS-targeted therapies, immunotherapy, brain metastases, and the critical role of patient advocacy. A powerful conversation filled with hope, insight, and the future of cancer treatment.
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Getting the information to make the best set of decisions is extremely important because you that first step can make all the difference in the world. We started to realize that there might be lots of small groups of patients. And if we could start to carve uh these pieces out, we could start to make uh meaningful progress for patients. Cancer isn't just in the cells where it started, it changes the entire environment around it. And so essentially now the tumors are unmasked. And in that setting, then the T cells and the other cells uh in the immune microenvironment can frequently recognize the tumors. And so that provides uh an entirely different way to treat cancers this is called immunotherapy. These sorts of treatments have been an enormous game changer. We're making really good progress in my cancer.
SPEAKER_01Welcome to the Hope Forward Podcast. I'm Lisa Spain, and today I have a super special guest. But before I make the introduction, I want to tell you a little bit about him because he's truly amazing in his field. First of all, he graduated from Harvard University in 1993 with a degree in biochemistry. He obtained his MD and PhD degrees from Albert Einstein College of Medicine. And he also performed his clinical residency at Baylor College of Medicine before joining MD Anderson Cancer Center in 2006. My special guest today is Dr. Don Gibbons. He's a physician scientist, specialing in lung cancer medical oncology. His lab is all about investigating the unique characteristics of tumor microenvironments in lung cancer. And what are the mechanisms that drive cancer cells to leave the primary tumor and spread to other areas outside the lung? He's received so many different awards, including being selected, the Physician Scientist Award. Dr. Gibbons is the director of Thoracic Head and Neck Medical Oncology Translational Genetic Models Lab and the co-leader of the lung cancer moonshot program at MD Anderson. Based on that, is it fair for me to say that you truly are working on opportunities for therapies for patients, actually bring to life how they respond to lung cancer?
SPEAKER_00Well, thank you, Lisa. That was uh an overly uh generous introduction. I I really appreciate it. Uh to get right to your question, though, yes, you know, here at MD Anderson and in our uh Department of Thoracic Head Night Medical Oncology, you know, that's really our goal uh is to enhance our understanding as much as possible of these diseases so that we can really be bringing forward uh new treatments all the time for our patients.
SPEAKER_01That's so huge. Obviously, that's our audience today, right? Is our patients. And we really my goal in the Hope Forward podcast is to make sure that as best we can, we always are informative and bringing educational insights. That's why I was super excited about today. So obviously, you've had this amazing, incredible academic journey from Harvard to MD Anderson. Can you just tell us a little bit about what first drew you to lung cancer research?
SPEAKER_00Yeah, I have to say I've actually had a fairly circuitous path. You you covered about uh 25% of it. Uh there was a time when I was gonna do something else entirely. In fact, uh my PhD is in molecular virology. Uh, and when I grew up, I was gonna be an infectious disease expert and and work on viruses. So, and that was 25 years ago. So you can imagine what my life would have been like in the last five or six years if I had gone down that pathway. Um but but uh a couple of things happened in my life uh to convince me otherwise. Um, and and those all converged uh when I got here to Houston. Um my wife and I moved here from New York after our training. Uh and uh when I was doing my residency at Baylor, I very quickly realized that I did not enjoy um uh infectious disease as a specialty. Um there's not, for most of the patients, there's not a lot of long-term interactions. Many of these are folks who just have some kind of infection. And once it's cleared up, you know, you really don't see them anymore. Uh whereas on the flip side, when I was taking care of oncology patients, I really quickly realized uh the opportunity uh to have a really lasting impact in their lives. And and in many cases, these are these are very long uh interactions with the patients, with their families, you know, through everything that they go through. Uh and that that sort of medicine is is really what I had trained for and what I was much most interested in. Um so then I came here to MD Anderson. Uh and and here at MD Anderson, uh again, I very quickly realized uh the type of patients uh that I was most drawn to and the type of science that I was most drawn to. And remind you, you know, this is 20 years ago, so it's the mid-2000s, um, and we just had uh an inkling uh that there could be uh some real uh progress made in lung cancer, which is an incredibly aggressive disease in many cases. And at that point, 20 years ago, we just had chemotherapy. There was one targeted drug, or LotNEB, or Jefit neb, um uh targeting EGFR mutations, and that's all that we had. But there were really unbelievable successes in a small group of patients. And so that's when we started to realize that there might be lots of small groups of patients. And if we could start to carve uh these pieces out, we could start to make uh meaningful progress for patients. And so this, both as a physician and as a scientist, was was really an exciting area for me uh and just drew me in uh immediately.
SPEAKER_01Well, it's you know, in the long term of our relationship too, as long as we work together. I mean, it's it's 20 years this year um since Rexana was diagnosed, but it is amazing to me to see the difference. It was kind of like a cold stretch of desert land, you know, from 2006 to we got to 2009, 10, 11, 12, you know. And then now what's happening in research, it is absolutely blows my mind. And I'm so thrilled. It just people ask me all the time, you've been doing this 20 years. I'm like, I couldn't be more excited today and just more, you know, I don't know how to even explain it, more desperate to really lean into supporting research than ever. So you kind of alluded to this a little bit of your interaction with your patients, and that it really drove the heart and soul of where you're at. How does your relationship with your patients shape the questions you ask in your lab? Or how do you navigate that?
SPEAKER_00Yeah, it's it's it's sometimes a hard balance because um you can't every observation that you take from the clinic or with interactions with patients, not all of those can be taken back to the lab. There's not enough time, money, or hours in the day uh, you know, to really do all of these things. So you so you have to try to choose uh the things that you think are going to be most meaningful. Um and for me, it it's usually come down to either really important areas of opportunity where there's clearly uh some sort of ground shift going on in the field where we can have an impact. And and and we will try to take those back to the lab. Now, sometimes that's directly you know in my lab, and and we will work on that because it might build on an area of of strength and prior research that we have. Um, or we will work with junior faculty and others uh in our department or either collaborators elsewhere uh to try to really jump in on things that that look like uh like important opportunities. Uh at the same time, um we we also try to play the long game. And by that I mean we try to predict out, you know, where are the changes that are most needed, um, where if if we have long-term sustain efforts, we could make real impacts over time. Um and so it's it's really kind of a mix of those that that drives the sorts of questions that that we bring into the lab.
SPEAKER_01I think that mix is critical, right? Because it goes back to what I said a minute ago. I mean, obviously for us in patient advocacy, we're wanting immediate, right? And we need it, we need it now. Um, but also I have a new appreciation over the years at what investments 10 years ago did in the lab to what's happening today. And um, I'm constantly finding myself encouraging people, listen, what we're see receiving today is because of investments in research and scientists leaning in 10 years ago.
SPEAKER_00Right, right. And and even further back, you know, just a really simple example. When you go back to 2006, when you go back to the mid-2000s, we we just, as I indicated, we had, you know, a single kind of inhibitor for EGFR inhibitors. Um, it took us the last 20 years to to really figure out how best to use those. We're still refining those uh today, but but just as or even more importantly, all of the lessons that we have learned over the last 20 years for EGFR mutant disease and how to use those inhibitors, we have then successfully and successively applied to multiple other uh types of lung cancer, whether it is alk-driven lung cancer or ret-driven lung cancer, or now KRAS-driven lung cancer is the KRAS inhibitors are coming online. So again and again, uh we're we don't necessarily have to relearn all the same lessons. And our development in these new areas can be quickened significantly by the lessons that we've learned from our prior iterations and other similar diseases.
SPEAKER_01Absolutely. Well, uh you know, I know you study the tumor microenvironment, right? And can you just kind of tell us in simple terms why that matters for lung cancer patients?
SPEAKER_00Yeah, so you know, first and foremost, just what is the tumor microenvironment? The way that I describe it for folks is that it's basically the neighborhood uh that the tumor cells are in, right? All normal tissues have a really highly regulated neighborhood. Um the interactions with other surrounding cells, interactions with the immune system, interactions with the blood supply, and what have you. And that's really part of how organs work so beautifully, um, is that they are self-maintaining in in a really uh you know, in a really elegant sort of way. But cancer disrupts those. And cancer isn't just in the cells where it started, it changes the entire environment around it. So now it's getting blood supply that it shouldn't have gotten, it has bad interactions with its neighbors, and and all of those then basically form a small uh new sort of tissue or a new sort of mini-organ that is is really very selfish to the overall uh organism. Um, and as and as a consequence, you know, that's that's where all of the the bad things come from in terms of how cancer affects and affects our bodies. You know, the other thing that's really important about the tumor microenvironment is that um because it changes the blood supply, because it changes the oxygen levels, because it changes so many different things about how uh about the environment that those cells are are now in, it then also can change how they respond or don't respond to certain therapies. Um so the way that a normal cell would respond may be quite different than the way that a uh an abnormal tumor cell, but also in a really messed up neighborhood, uh, might respond to a treatment.
SPEAKER_01Yeah, I I find it so fascinating. I could go down like rabbit trails just listening to the conversation because I can see how when you're trying to understand how these say cells respond, there's so many different dynamics to look at. I mean, it's crazy. So what we hear about cancer spreading, and of course that's a fear factor for everybody when it begins to spread. Can you really talk about um just in layman's terms for me to help me understand how the cells leave the lung and form a tumor somewhere else when it's spreading?
SPEAKER_00Yeah. So um, you know, a lot of it comes back to this idea of the neighborhood and of the normal tissue architecture. In in that normal architecture, if a cell becomes sick or if a cell becomes precancerous or if a cell becomes infected by, you know, bacteria or virus or what have you, there are normal mechanisms of response uh by the immune system, by surrounding, by the surrounding tissue, so that those so that those cells should be wiped out and there should be a normal healing process that occurs. But in cancer, as as the cancers become more aggressive, um divide more and more and start to mess up that environment around them, they now gain access uh in uh to the to the blood supply or to the drainage and to the lymph nodes that they normally wouldn't have. You know, normally these most of our cells are not migratory. You know, cells of the lung, for instance, aren't normally migratory, cells of the breast, uh, cells of the pancreas or the GI tract aren't normally migratory, and and but in the form of when they become cancerous, uh, they can change how they behave. And in that messed up environment, they can now get access to the lymph node drainage or get access to the blood supply, um, the veins, the arteries. Um, and when that happens, then they can circulate to other places in the body. Um, and then that's where they can then set up shop and colonize uh a distant metastatic site, whether that's in an area of bone, whether it's in the liver, whether it's in the brain. Um, you know, unfortunately, lung cancer can be quite metastatic. And I've seen it go just about everywhere in the body except for probably the fingernails. Um, you know, we've we see patients who have who can literally have metastasis just about anywhere. Um, and and so that's you know one of the things that we keep a close eye out for and try to jump on early.
SPEAKER_01Yeah. So your research really highlights how tumors can suppress the immune system. So can you talk to us about why that's such a critical part of treatment success?
SPEAKER_00So, you know, this is something that's been known for a long time, for decades, that that tumors can be immunosuppressive. Um but it was something that we couldn't do anything about, or there was no way for us to leverage that, you know, that part of the tumor microenvironment, that part of the neighborhood. Um but in the last 20 years, um, you know, due to the efforts a lot of a lot of uh really uh you know smart uh immunologists, people like uh Jim Allison and others, what we have realized that the is that there are ways that we can um reverse that suppression. So many tumor cells um either make things uh or they express things on their surface that will uh blunt or turn off uh the response of normal T cells or other immune cells in the tumor microenvironment. Um and so now what we have is is the opportunity to give treatment to patients that will reactivate uh the immune response. So essentially, uh, you know, these tumor cells can have a shield around them that prevents the T cells from recognizing them, or sometimes I refer to it as a cloaking device. Um and you can give them these drugs, they're usually in the form of antibodies, um, that will um stop those interactions. And so essentially now the the tumors are unmasked. And in that setting, then the the uh T cells and the other cells uh in the immune microenvironment can frequently recognize the tumors. And so that provides uh an entirely different way to treat uh cancers. This is called immunotherapy. Um and these sorts of treatments have been an enormous game changer uh in melanoma for the last 15 or so years, probably a little bit longer, uh, and in lung cancer for about the last 10 years. Um and one of the reasons that these are such a game changer is because you're teaching the immune system to recognize the cancer. And your immune system has memory. So if you've had the shingles vaccine, or if you've had COVID, or if you've had the flu, or if you've had a bacterial infection of some type, your immune system can develop an immune memory over time. Um, and so you don't have to continuously take antibiotics to treat those those things, or to take antivirals to treat those things, if your immune system can recognize them. We have discovered that the same thing can be true of cancer. If we can teach uh your own immune system to recognize the cancer, and the cancer is not shielded by these various mechanisms, then uh the the immune system can keep the cancer in check or completely destroy the cancer. Um and so the the very best long-term outcomes that we see uh for for many of our patients are those who have had immunotherapy, where the immune system has clearly recognized the cancer and either continuously keeps it in check or or has completely wiped it out.
SPEAKER_01So Okay, I want you use T cells all throughout that conversation. So can you just explain to us a little bit so uh our patients can understand what are T cells and the role that they play?
SPEAKER_00Yeah, so your immune system has multiple components to it. Um, and and in the blood, you have several different types of cells. There's red blood cells that obviously carry oxygen, there are platelets that help you uh to clot so that you don't bleed if you if you have an injury, and then there are the white blood cells that we we generically refer to those. But within the white blood cells, there are multiple different subtypes of immune cells, and those are what are really the little soldiers that that fight infections or that can fight cancer. And T cells is is is one of those subsets. And T cells can be because uh they recognize one thing, and and that's all they ever do in their entire life is recognize one thing and destroy that one thing. And it can be a virus, it can be a bacteria, it can be a cancer cell. And so if we can build upon what your normal immune system should normally recognize and normally fight, then that's where we have the best chance over the long term of maintaining a balance between uh you know any any cancer cells in the body and and and the normal cells.
SPEAKER_01Okay, all right. That's a great explanation. Thank you so much. I love those little soldiers when they're attacking. Yeah, yeah. That really makes me happy. Let's talk a little bit about um KRAS because I know this is an area that Rexana's foundation has supported some of the research. And um, you know, for years KRAS mutations were really considered very undruggable. Um, can you talk to us about a little bit how that has changed in recent years and even why KRAS is kind of challenging?
SPEAKER_00Yeah, so so just to start at the beginning, you know, KRAS is a gene in our cells, um, and it makes a really important protein. And and the analogy I give folks is it it's essentially a light switch uh for cells. So KRAS has a normal function, and very frequently uh you know it should get turned on and get turned off uh based upon how a cell senses normal signals in its surrounding environment, right? But if if it's mutated, uh which can which can happen in a broad range of cancers, in fact, it's it's one of the most mutated uh cancer genes in any cancer type. Um and if it's mutated, then essentially the the light switch is broken. So if I walked over to the wall there and took a hammer and and and broke that light switch while the light is on, it would stay on and I'd have no way of turning it off. And that's the same thing that happens when KRAS is mutated in in cancer cells, is then the cells are always on. You can't you can't turn them off. There's no normal way to turn them off. And and we've known this for for decades. Um, but it's a unique type of protein that as a protein is very hard to develop drugs against. Um, and that's based upon some of our old ideas about uh how drugs work and and and the types of drugs that can bind to a protein. Um but in the last decade or so um there have been a number of realizations and some really unbelievably innovative chemistry that has taken place. Uh one of the first things that that was realized is that uh K-RES exists in different forms. It turns on and turns off. And as it does, um then there are some transient pockets on the surface of it that get uh that get opened up. Um and so as a consequence, the the drugs that were initially tried years ago were for just one form of it, but not uh but didn't try to target it during this dynamic change. Whereas the newer drugs do that, they go after these pockets that open up during the dynamic changes. Um that's been one thing that's been a real game changer. Uh the other thing that's been a real change uh is uh the overall concept uh in drug development of just trying to go after a protein. Now some of the very best uh RAS-targeted drugs don't just try to bind RAS, you know, so it's a relatively small protein, it doesn't have a lot of pockets on it. But now uh drugs uh such as uh what we uh refer refer to as molecular uh glues, for instance, uh they they bind to RAS, but in addition to that, they then bring in a much larger protein uh to form these larger tricomplexes. Um, and those are really very stable. Um so trying to target something that moves around a lot, um, that changes a lot all on its own is hard. But if you can uh put basically, you know, a small molecule on there and then bring in a larger protein, and now you have a complex uh that is much more stable, um then that's something that's much easier to turn off. Um and so it's it's been approaches like this new drug development, new chemistry, uh, new observations on how the protein actually works that it that have allowed us uh a myriad of new approaches actually to try to target RAS. And and many of these have have come into the clinic or are on the verge of coming into the clinic.
SPEAKER_01Well, that was what I was just about to ask, because I know there's been great progress, but how close are we to turning the KRAS targeted therapies into real solutions for our patients?
SPEAKER_00So we we have two approved drugs. Um they are for a very specific form of K-REST mutation, the K-Rash G12 C, as in Charlie, a C mutation. Um and part of that comes down to the chemistry of that C, uh, which that I that I won't go into. Uh, but there can be many other mutations at that 12 position or at the 13 position or at the 61 position of of KRAS. There can also be mutations in other similar uh proteins. Uh, besides KRAS, there's NRAS, there's HRAS. Um, and so what has happened now because of the new chemistry that has emerged around KRAS is people uh at various companies and academics have been developing uh inhibitors that recognize all of the KRAS mutations, not just G12C, but the others. Uh those that recognize not just KRAS, but recognize all of RAS, the wild type RAS, the mutant RAS, uh all that recognize uh HRAS, NRAS, et cetera. So so there's just been an explosion of uh literally hundreds of drugs that have been developed to go after one version of RAS or another. Um and like I say, there are only two that are FDA approved. There are others that are very close. Uh for instance, this weekend, and I think you'll get to this a little bit later, but this weekend at the ASCO meeting in Chicago, there was an unbelievably important announcement of a phase three trial in pancreatic cancer. Now, in pancreatic cancer, they also have KRAS mutations. They're usually KRAS G12D. It's about 90 or 95 percent of pancreas cancer that has those. Um, and there was a new drug that was that that has been tested with unbelievably good uh results. Um, and and this is important because this is a drug that is a pan RAS drug, so it recognizes many of the different RAS mutations, uh, which means that these data in pancreas are unbelievably important to the colorectal uh teams and all the colorectal patients. It means that it's important to all of our uh KRAS mutant non-small cell lung cancer patients and many patients with many other tumor types. Um, so the the progress in in one area is clearly uh uh leading over into these others. And so we're very, very excited about that particular drug, but also many other drugs in this space uh that are absolutely going to be game changers over the next months to years.
SPEAKER_01And I know you've heard me ask over the years, and I'm always trying to understand how we're learning from other cancers. And it always feels like to me, with obviously already in your conversation, all the different types of lung cancer, it seems like there could be so many different ways that other cancers can learn from lung cancer, you know, and how it plays a role. But I is it just me, or are we evolving and moving to where there's so much more shared information where we are learning from each other? Um, or has that been going on for a long time and now it's just because there's so much more social media and all that we're hearing about it?
SPEAKER_00I I think it's a mix of both. I mean, in general, in clinical oncology and cancer research, there's always been uh an openness to share, to collaborate, you know, across institutions, across tumor types, across borders. Um, you know, we we really have always done everything that we can to learn from each other. Um but I do think that in today's world, it's significantly easier uh to collaborate. It's much easier to run a large phase three trial across the globe. It's much easier to collaborate with people in in other countries uh right now. Um and in addition to that, um the uh the the you know what uh lay people or folks who are who don't do this every day for a living uh are have access to in terms of very rapid dissemination of this information, you know, that did not exist. You know, when I was a fellow 20 years ago, you would have to go to a meeting like ASCO to know what had happened. Um now uh you can literally get online and in a matter of minutes see most of the major presentations at ASCO on YouTube or on one of the other platforms, right? So, so so you know, our attitude has not changed. The pace at which we've been able to do things has certainly accelerated, and our ability uh to disseminate information, just like on this podcast, right? Podcasts didn't exist, right? So our ability to get this information out faster to everyone, not just the folks who who do this every day, uh, has accelerated uh as well.
SPEAKER_01You know, um that brings up another topic for me because when um Rex Anna was diagnosed in 2006, you know, uh you would have very little information. It was all negative, it was all online. And that's one of the reasons why I wanted to start this podcast is to make sure now we have a plethora of information, but ensuring the information is accurate, it's educational, and it comes from a place because there's a lot of people talking about different things, but uh I wouldn't even want to be sitting here having a scientific conversation about KRAS and ways to address that without a scientist online. So I think that's one of the reasons why I'm bringing this because I want to make sure the information's accurate and um especially at the speed people are getting it. I think that's critical.
SPEAKER_00Yeah, I I couldn't agree more. And and I always tell my patients and their families, just be really careful where you get your information. Um, and you know, it so long as you have an open dialogue with patients, then I then I think that that works. Um, you know, I very frequently will have patients bring information to me that they have found online, and sometimes it is not accurate, or sometimes it's very accurate, but it absolutely has nothing to do with their cancer, right? You know, I I tell folks that lung cancer is probably a hundred different subtypes. And if they have alk-driven lung cancer, it may have no relationship whatsoever to somebody else who has lung cancer, but it's small cell, or somebody who has squamous cell cancer with very different changes in it. So, so so there can be a lot of subtlety. And and so either the information online can be wrong or it can be misleading. There are people that just want to sell you stuff, that's for sure, sure the case. Um, uh, or or it may just not apply to your specific situation. And and that's you know, it can be just as important. You may have very good information, uh, but if it really doesn't matter to you, right? If if if I drive a Toyota and I'm reading all about the Mercedes and how to fix a Mercedes, it may have nothing to do with my Toyota.
SPEAKER_01Right. Yeah, I think that's critical. And I try to let people know because one, it can be a fear factor when you get all this social media, but another, it can drive information that's not accurate. And so I really wanted to make sure we had a space where we were providing accurate information. Well, let's talk about another area. You know, this is an important area for our board and and supporting research, and that's really leaning into and targeting these brain meds. And can you talk to us a little bit of why that is such a difficult area in lung cancer and research um brain meds?
SPEAKER_00Yeah, I would say in many ways, you know, we see this as you know one of the next upcoming frontiers. Um you know, we just talked about the successes and some of the targeted types like EGFR and ALC, now increasingly KRAS. Um but one of the areas uh over you know all the years that we've been treating patients that that is problematic is when uh they develop uh spread into the brain, uh brain metastases. And that can either happen in the the tissue of the brain, uh, what we we will refer to as parenchyal metastases, um, or it can happen in the lining that is around the surface of the brain and the spinal cord uh where the cerebral spinal fluid or the C CSF is. And when that happens, we call that leptomeningal disease because those uh that that lining of the leptum meninges. And so involvement of either of these, the the brain tissue proper or the leptomininges, uh, can uh can cause uh you know real havoc uh for for somebody. Uh they can be very, very symptomatic uh from these. Um and historically the treatments for brain metastases and leptominingal disease are quite poor. Um and so the the overall outcomes for patients who have developed these can can often be extremely poor. And and even for patients who have done really well over the long term, um, you know, we know that for patients who uh are long-term survivors on EGFR inhibitors, on alk inhibitors, many of these uh targeted agents, uh the incidence of brain metastases uh goes up over the years. So if they're five or six years out, um there is, you know, an unfortunately high chance that they could develop brain metastases. So as we develop more uh and more effective uh therapies uh to treat disease everywhere else in the body, um, we have to make sure then that we're keeping an eye out for brain metastases, trying to prevent and stop them early. Um, but we also now need to take this as the next frontier of developing ways uh to really monitor for uh and to really treat brain metastases more effectively.
SPEAKER_01Right. So um I'm not gonna get into it now, but I see I have a whole list of questions that I'm thinking about. Um because you know, what where should a patient go? Um should their conversation be with their doctor when you're talking about these brain meds? Because even I was sitting in sessions all last week at ASCO, you know, whether what the treatment should be for the brain meds and the consequences of the different treatments and all that. So um how how does a patient put together a team or what are some of the questions they might would ask when they are dealing with brain meds? Can you provide any insight that we could give our patients because a lot of them are dealing with this and the fear has escalated so much? And I think there's a lot of hope, but I think that they've got to have the right team in place, the right questions to ask.
SPEAKER_00Yeah, I I think the single most important word that you just used uh is team. Right. So this is a situation. I mean, overall, what we deal with in lung cancer, lung cancer is a really multidisciplinary uh you know sort of uh uh treatment area. Um we really rely on our surgeons, we really rely on radiation oncologists, we really rely on the pulmonary teams, et cetera, et cetera, right? So we have to have a lot of people uh in there to to most effectively manage what all of our patients are dealing with. And that that's regardless of where the disease is. But I would say that's especially true when we're talking about uh something like brain metastases or leptom meningial disease. Um, the approaches that we have rely very heavily on radiation in many cases, uh, whether you know somebody has a single or a couple of small metastases in the brain, and that's a situation where the radiation conteam can use stereotactic or focused uh sort of radiation and therefore avoiding surgery uh and the long recovery from surgery and what have you. Or maybe if somebody has a big area of tumor, uh they might be symptomatic or have seizures or something along those lines, a lot of swelling in the brain, that may be a situation where uh getting uh the surgeon involved and and either uh releasing uh that pressure or or actually uh taking out uh the area of tumor uh is important, uh, while at the same time we're coming up with systemic therapies, either oral agent or IV agents that get into the bloodstream and get delivered everywhere, including into the brain, uh, to try to uh you know prevent either these from growing back or to to shrink these down. So this is a situation where we we try to bring together uh you know all the tools that we have across the various teams. Um, but but that's why it's so important because by myself, it would be very difficult, you know, to manage all the things that a patient and their family might be dealing with. And so that's where we really need to have others involved. Frequently we we get the neurologist involved, you know, et cetera.
SPEAKER_01Yeah, I think that's so important. And obviously, as a patient advocate, I'd want to make sure our patients understand that they need a voice in that conversation. They need to really understand what's going on and not be hesitant to ask the questions. Well, um, I've mentioned Rexana's foundation as far as our passion about um research funding. Can you just speak a little bit about how important philanthropic funding is to accelerate discoveries? Because obviously, just like what we were just talking, there's a lot more work to be done. And I want us to continue to lean into that. And I'm very passionate about that. So can you talk about that just a little bit?
SPEAKER_00Yeah, absolutely. I mean, you you've heard me say this a million times, but you know, I think that the uh money that comes from philanthropy is so incredibly important, and it is for lots of reasons. Um, but I'll try to outline a few that I I think are at the top of the list. The first is just a question of timing, right? We've been talking, you know, continuously about time. You know, that's all that our patients think about is time. How much time do I have? How much quality time do I have with my family? These sorts of things. How quickly can these drugs get to me, et cetera? And the same thing is true on the research, on the research funding side, right? I mean, everything that we do is enormously expensive, all the research that we perform, and um it's increasingly difficult in today's world, especially, um, to get research dollars. Um, you know, the changes of the NIH, the changes at other uh big funders who fund big grants, um, those can be hard grants to get. But then once you get those grants, you're usually fairly locked in uh in terms of what you have said you're gonna do. So if you get a five-year grant from the National Cancer Institute, uh uh National Institutes of Health, um then you have to do exactly what you said you were gonna do in that grant, unless there's some really, really unbelievably good justification to make us a small pivot. Um but is as quickly as the world is changing in science and in medicine, and is and with the way that we see opportunities arising, if there is a real opportunity for us, uh we may not have the year or two that it takes to write a grant, revise the grant, get it submitted multiple times, and then finally get it funded before that opportunity disappears. Uh so the funding from Rexana, the the funding from other philanthropy groups uh can be really important uh for us to jump on these opportunities as they're coming up and to provide that initial preliminary uh data to either prove a good idea or to disprove an idea that wasn't good. Um and either way, it's a win-win, right? If we jump on something, you know, spend the seed money and prove that it was something that we shouldn't have followed, then we can cut our losses and move on to the next good idea. If it was a good idea, then we have the preliminary data in place, we have the groundwork in place uh to now go out uh and to try to get bigger, uh, you know, longer-term grants over multi-years uh to continue to support that effort to really bring it forward to our patients.
SPEAKER_01Yeah, I think that's so important is giving the opportunity for these great ideas and what the science is leading you to to really be a catalyst, right, for the future change and the future needs that we have. Um, man, I can't emphasize it enough because I just want to keep getting the funding to you guys so you can keep doing the work. I want to kind of switch gears here a little bit. I know I've been just diving into so many different topics, but I want to talk a little bit about immunotherapy and resistance. You talked about alluded to immunotherapy and the game changer it was years ago, but um immunotherapy doesn't always work for everyone. Can you kind of explain why some patients respond and some don't?
SPEAKER_00Well, I can explain a little bit. I mean, this is still a very active area of research, and this is true in lung cancer and many other tumor types. Um, there are some tumor types that respond really well, there are some that don't. And uh within tumor types, there are some subtypes that respond and some subtypes that don't. So this is an area of just continued uh constant work uh for basically all oncologists and and most folks who are working on cancer biology. I would say specifically in lung cancer, what we have learned is that there are some types that appear to be what we call immune cold, uh, meaning that the immune system doesn't seem to recognize them very well. So if you look in the tumor, the immune system is just not in there. The T cells aren't in there. So many times in those cases, if you give somebody immunotherapy, at least the immunotherapy we currently have, it doesn't do anything because the immune system just doesn't see that tumor. In other cases, uh, for instance, we were talking about KRAS, there are some subtypes of KRAS that have other mutations that go along with the KRAS, such as an SDK-11 mutation, a key mutation, some of these commutations. In those cases, the cancers seem as though the immune system recognizes them, um, but it's the wrong type of an immune response. So it's a kind of a suppressive immune response. And so that's a situation where the immunotherapy often doesn't work particularly well, at least the way that we've been giving it. And so what we've learned in those cases, for instance, is that just giving uh some of the single agent immunotherapies that we have doesn't work well, but giving combination immunotherapies of an anti-PD1 and an anti-CTLA4, often with chemotherapy, for instance, that some of these combinations work better. So we're learning more and more about the different subtypes. Um, for instance, small cell is one that historically has not responded well to some of the single agent therapies either. However, there have been game changers in the last couple of years of something called a T cell engager. That's a situation where there's an antibody that recognizes a protein that sits on the surface of the small cell uh tumor cells, and then specifically also grabs the T cells as they go by and brings them in. So that's a situation where the T cells don't have a choice. They're basically being dragged in and being matched up directly by something that's already binding to the tumor cells. And and that has been enormously successful in small cell. Um so we are learning uh who seems to respond, who doesn't. Um, we're you're starting to learn more and more the whys uh in those subgroups, and then also starting to develop some strategies in each of those subgroups, about but we still have uh a lot more work to do.
SPEAKER_01So, you know, uh that leads me to another question that that comes up a lot. And um everybody that knows me knows I'm a huge advocate of MD Anderson and the Thoracic team there. I believe in you guys, the work you guys did is tremendous. You guys are the leaders in the world in thoracic. And so when I think about all these patients all over the place, I'm always recommending a second opinion if they're somewhere they need to be reinforced. But one of the reasons why I want to bring this up and the question I have for you is that isn't there a particular order that's more important or in lines of treatments that you receive, especially when it comes to immunotherapy, because so many patients I'll talk to and they're like immediately they're told by their doctor, oh my gosh, we need to start you on chemo immediately. And instead of getting a second opinion or determining what to do, that occurs. So do you have some suggestions in response to that as far as um the order of things or second opinion? I'll just leave it open to your comment.
SPEAKER_00Yeah, I I I think that you know, I'm I'm an advocate of having a complete picture before making decisions. Um and uh and I very much agree with second opinions. Um and and so you know, very frequently what I will see is that somebody comes from the community and there's a very and they may have been told in some cases uh to get started on chemotherapy or to get surgery or what whatever the recommendation was, but they're still an incomplete picture. They haven't had all of their imaging, so I don't actually know if their staging is correct. We don't have their molecular profiling back yet, so I don't know that if they have one of these targetable mutations in EGFR, an ALK or RED, a KRAS or what have you. Um I don't know what their commutational status is, I don't know what their PEL1 status is, so I don't know if immunotherapy is appropriate for them. So often I find uh when folks are coming for their second opinion, uh there are still lots of gaps uh in the specific information about this patient. So many gaps that I would not be able to make what I think are an appropriate set of treatment recommendations. There are also situations, and I actually saw one of these last week, where somebody has something that's potentially actionable, um, but they have set up second opinions because they want to see if what is currently available is the best choice or if a clinical trial is a better choice. Um this was uh, for instance, a situation where somebody was coming from uh another uh big city, uh, but a big city that doesn't have a large thoracic group and doesn't have many trials. And uh they'd had some prior immunotherapy with some limited success, but they had a particularly rare mutation. And the question was whether or not they should get one of the standardly approved drugs and would it work in this situation, or or would they be better served on a clinical trial? So I saw them last week, we discussed various options. They're actually getting a third opinion uh up in New York uh this coming week. Um so they're gonna see you know what all of their options are. And and and I think that that makes sense because at the end of the day, um what someone needs is is very dependent upon their disease and what decisions uh they are comfortable to make should be based upon a complete picture uh where they have. All the options laid out for them because the decision that one person makes, one patient, is not necessarily going to be the same as the next patient. And so they have to have the information to make good decisions that they're comfortable with because these decisions are going to affect them, gonna affect their lives, and affect their families.
SPEAKER_01Yeah. So um I'm speaking as a patient. So if a patient's in front of you and they're like, but I have lung cancer, somebody's told me I have lung cancer, I'm panicked, I want it out of my body, I want to get started on something immediately. Like um, what about the time frame? Because that's normally where the conversation comes in. Do I have time to wait on a second opinion? Do I have time? So can you just speak a little bit to that, to the time of as soon as they're diagnosed, do they feel the need they have to start something immediately for the urgency or the time factor for those second, third opinions to really understand the disease?
SPEAKER_00Yeah, no, I I completely agree. This does depend very much from one patient to the next. I mean, we get patients who walk in our front door and basically should not be seeing me. They should go straight to the emergency room and be admitted to the hospital, right? They are so sick from their cancer or a secondary problem that the cancer has caused that they need to be in the hospital, right? Now, that may be a situation where uh uh they can be stabilized and we can still take the time uh to learn more about their cancer and fill in the gaps and make a good set of decisions before we start their first treatment. Or it may be a situation where we do need to do something to treat their cancer with chemotherapy, or maybe you know, sometimes we give upfront palliative radiation if somebody's having a lot of bony disease or a lot of pain or something like that. So there are situations where something does need to be done now. And by now I mean today or this week or you know, in the next few days. Often, though, that's just a temporizing measure for us to still buy the time that we need uh so that we can get the rest of the information in place for a long-term plan. If if somebody is is well, though, I mean, I we have plenty of patients who are diagnosed who are not really sick. Like you would never pick them out as the patient in the waiting room. And then that's great, right? Their cancer is not yet making them sick. In those situations, getting the information to make the best set of decisions is extremely important because you that first step can make all the difference in the world. Unfortunately, we do see cases where patients have not been treated appropriately up front or not all the options have been laid out for them. And so they might jump into a therapy that may not be the very best choice for them. And so we, you know, we do uh recommend. Uh, you know, in our case, you know, we very frequently will see a patient within a few days to a week of them calling in to get a second opinion. So I, you know, this should not be weeks and months uh in waiting. Um, but you know, taking a few extra days or a week or two to get the additional information so that we really know what we're dealing with uh can can make all the difference in the world.
SPEAKER_01Yeah. Thank you for that. Yeah, I think that's so important because you do you hear the words that you're diagnosed with lung cancer, you do feel this panic, this urgency, which is all fair, but really trying to navigate the disease when you are very specific to the long-term opportunities. Thank you so much. So recently I attended AACR and we also just talked about just last week. I mean, I got back yesterday, last night, from ASCO in Chicago these conferences. Can you talk to us a little bit about what makes these conferences so important to cancer research across the world?
SPEAKER_00Yeah. Um, so to give some perspective on on what these are, you know, this isn't, you know, uh you know, tens or a few hundred people meeting, you know, in in the holiday inn and uh, you know, uh in Lumbock. Um, you know, the one that you were just talking about, ASCO, that was in Chicago last week, had about 40,000 participants from all over the world, right? So when you think about what that means, that means that uh the very best academic doctors and research, the very best community physicians, uh company doctors, uh company executives, company scientists, the regulators from industry, FDA, uh the NCI, et cetera, patients, patient advocates, right? I mean, everybody who's an honest to God stakeholder in any type of cancer, right? I mean, I normally if I go to a small meeting, I don't go to a breast cancer meeting, I don't go to a colorectal cancer meeting. But at a meeting like this, every single cancer type, big, small, or otherwise, is represented. And so the nice thing then is that you have this critical mass of all these people who are spread out all over the world on a normal daily basis. And even with the hyperconnectedness that we have in today's world, there's nothing like getting 40,000 of your best friends who who all work on cancer, who all take care of cancer patients, who are all involved in this in the same place talking about the same things. And and so um, you know, this is literally our our education, right? When I finished uh my training 20 years ago, you know, if if my education stopped there, I wouldn't know what to do in today's world because everything has changed. And so this is where we all go uh to get our constant updates on what's happening in every tumor type, uh, what are the results, good, bad, or not, of all the trials in our cancer type and others, what's working, what's not working, if it's not working, why? If it's working, are there toxicities we need to be aware of? Um, so so you know, this is just uh, you know, this being together in this community and meeting on a regular basis uh to learn from everybody else uh is is just you know our bread and butter. That's what we have to do.
SPEAKER_01I know over the years, to me, the energy was palpable. It's like crazy at this event. Um I also will say that since probably, I don't know, it was 2009, 2010, we had more major lung cancer announcements that were amazing. And I was, I I go to other sessions too because I'm always interested in the overlap and to be in the room with the announcement of doubling the life expectancy for pancreatic cancer. The room was so emotional. Um, Rexana's foundation, you know, supports several pancreatic cancers as well on our Sandy's project hope. And so it was so hopeful to get to videotape that experience and to be there, you know. But I felt the same way in some of the lung cancer announcements. And I know we're kind of running short on time here, but I I do have were there breakthroughs or announcements through ASCO on lung cancer that you want all of us to keep an eye on, future state, or things immediately for the patients right now that we should consider?
SPEAKER_00Well, the one you just said is absolutely applicable to lung cancer, right? So that same drug uh from revolution medicine that doubled life expectancy uh in pancreatic cancer is uh in the late stages of testing in lung cancer. Uh, there's a similar RASLU trial in non in KRS mutant non-small cell lung cancer. Uh we expect that that will probably read out around this time next year. So it may be the ASCO plenary next year if everything goes well. But we do really think that that drug, uh uh along with many of the other KRS drugs that you and I spoke about before, is is really gonna be a game changer. Um, you know, there were updates in other places. There was an update on the lore-latinib data for patients who have alkal mutations. It was the seven-year update on that showing that there's still uh continued unbelievably good long-term survival for those patients. Uh, Dr. Byers from our group presented data in small cell lung cancer on one of the new antibody drug conjugates against CES 6. That looks like an unbelievably good drug. Uh, there were updates for patients who have RET uh uh uh mutations uh in early stage. So these are patients who have surgery and that go on cell percaptanib uh thereafter. Uh there were uh announcements on the ivanesimab drug. So this is the drug that combines an anti-PD-1 with an anti-FEGF. It appears with along with chemotherapy to be better than just chemotherapy with pembrolizimab. Um so basically across the board, um, whether they whether it's uh for patients that have particular mutations or patients who don't have target fold mutations, uh, there were a number of updates that look like uh you know we're making really good progress in lung cancer.
SPEAKER_01Yeah, I was even in a session um and it was crowded and full, and it was end of the day yesterday. It was the 4 45 to 6 o'clock session. And um in that session, it was really awesome because they brought together the surgeons, oncologists, radiologists. Um, Dr. Cascone was um one of the facilitators on that or presenters. And um I think that that's another place that's exciting for me to see for the future because you could see the debate still exists, you know, radiation surgery, when and the timing of that. But it was wonderful to see all of these amazing minds come to the table in that one as well. So a lot of exciting things, I think, um, across the board. Um so you know, um, I was blessed to be able to lead a research team where we presented a poster at ASCO and our response was really amazing. I was blown away. But I the reason why I bring that up is I'm just, you know, our goal is to continue to push the patient advocate voice. And I just want to know your thoughts and feedback on how important it is the work of patient advocates.
SPEAKER_00I I think it's enormously important. I mean, you know, we have worked together for two decades now, as as you said. We work with other other advocates as well, either directly or as part of our uh joint uh SPORE program with UT Southwestern. They bring their own advocates to the table. Um, you know, and and and I I think the work that you all do is important in so many ways. I mean, first of all, you are the voice back to us uh from the patients and their families, you know, when I mean they're they are focused on their individual fights, but but you all, you know, see that uh manifold and and bring it back to us in terms of a voice from the community of patients and uh and and families. And and that's really, really helpful uh and important. It reminds us of of what we need to focus on, it reminds us of where our priorities are. Um in addition to that, though, you know, it to especially in today's world where uh the economy is not particularly good, especially the economy of grants, and where it's important for the advocates to stand up and say, this is where society needs to be placing its money. This is, you know, these are the priorities that we the people, uh, we the patients, we the families, have for where research dollars should be going. Um and so, you know, that is increasingly important because, you know, obviously we we have a stake in this, but we only have a relatively small voice uh with the government, uh, you know, with foundations, with whoever funders might be. Um but as patients and families uh stand up, you know, that that voice becomes even louder and even clearer in terms of you know where our priorities should be.
SPEAKER_01Absolutely. I actually had a call this morning um with an executive who asked me, said, um, was the attendance down? What was the vibe at ASCO because of the pressure with the government, all the different things on funding? And I was like, listen, the whole world needs to hear how important that meeting was because there was great synergy and people were not hesitant to step in and saying, Great work's being done. And I think we need to shine a light on that, you know. And that's a tribute to all the scientists, physicians, doctors, surgeons out there that they're just keeping their head down and doing the work. It's our job and patient advocacy and the rest of us to make sure we continue funneling the funds to allow you guys to do the work. But um, I certainly don't think there was a single person in any of those rooms on announcements that they were inhibited because they're worried about you know what's going on. They still were doing the work. It was amazing. So um just briefly, again, I'm I have to bring up Rexana Foundation because you've been such an incredible partner for us and we're honored to be working and supporting your work. But this spring, we've had a golf tournament, we had a derby event that was in South Carolina that was so much fun. You attended both of these events. Can you share from your perspective why events like this are important?
SPEAKER_00I think they're important because I think community is important, right? And and as we were just saying, the community is not just the doctors and the researchers and us hanging out in our own little club. Um, it's really a community of all of us uh who have skin in the game in terms of taking care of patients, taking care of families. And one of the things that we've always loved about Rexana's Foundation is that it's that it's a it's about community, right? I mean, that's what what you all have built over the years is uh a community of of the families, of the patients, and uh, you know, the two arms of what you guys do, you know, or it's like holding hands with with the two sides, uh, right? I mean, you reach out and you take good care of the families and you love on the patients and you support them in every way possible with the rally cards and the prayer shawls and everything else that you do at this at the same time that that that that you the that you support us and and our research so that we can better take care of the patients, right? And so these these events you know uh continue to build that community. But then in addition to that, now that that community exists, um these events facilitate dialogue, right? And that's that's what we all need, right? Everybody has questions um and needs. Um, and so these events provide an opportunity for them to ask questions, right? Just like the format that we have right here, except that you know, the room could be full with other doctors and and other families and other folks from Rexana. And we're all in dialogue uh in a way that answers people's questions and enlightens them and allows us to agree, you know, where where should we be headed? What should we make as our priorities? What, you know, should we define as goals for the next six months, the next year, you know, so that we can have really positive impact. So that what you all have done to build that community and facilitate these dialogues, um, you know, that's that's really is w what's helping us, you know, to move forward and to make a real impact.
SPEAKER_01Yeah, we we're so excited too. Just a quick plug here. September, we are having the Houston Lone Star Huddle Up event, which is our big event. What's something that you would say to everybody that may have an interest in Rexana Foundation in the Houston area or even traveling about attending our big gala?
SPEAKER_00Well, I would say please come. It is a ton of fun. Uh I always go, my my family comes, my extended family usually, including my kids who are now big. Uh, but tell your friends, tell your family. It's really a a very, very good time. Um but then I would also say uh, you know, don't just come, but but come and either donate or get involved in some way. Um, you know, I mean, it is a fundraiser. Um, it supports patients, it supports our research, um, and but you know, so you can have fun and do good at the same time. Um, and that's what this event does. And uh if you don't want to donate, that's fine, but get involved. Uh Rexana is uh foundation needs help. Uh they need help at, you know, at all the stuff behind the scenes, uh, and not just at the events, but throughout the year. Um, so I I would recommend that that folks really get involved and just do what you can to uh support the community that you've built and support the cause.
SPEAKER_01Yeah, we look forward to that event every year. So excited about it. Um and I agree with you. Our goal is certainly to build that community and to be a resource out there to just encourage and love on everyone. So we're coming here to the end in each of our um Hope Forward podcasts, we kind of have a cadence. I do a three-to-one. It's kind of like the speed round, okay? So I'm gonna give you a speed round and um it'll go really quick, but if you just hang in there, let's do it. So my first one is the three. Give me three words you would use to describe Rexana's foundation.
SPEAKER_00Uh hopeful, uh community, and impactful.
SPEAKER_01Love it. Okay, two. Give me two areas in research that we need to be watching for in the future.
SPEAKER_00Brain metastases and KRAS.
SPEAKER_01Okay, good. All right. And then our one, I always like to leave everybody with an action item that our s listeners could do or something that they should take based on our conversation. What action item would you give them?
SPEAKER_00I would say you can help, right? We've talked about the things that we're doing, uh, but we need to build our community. And so I would tell every listener that in some way they can help. They can either ask their grandmother or their mother to get that screening that they haven't gotten because too few people get screened for lung cancer. Uh they can join our organization or one of the other uh organizations who supports lung cancer patients. Uh, they can help support research, right? All of us can do something. And if everybody just did a little bit, um then as a larger community, the amount of impact that we would have uh to you know cure this disease uh would be unbelievable.
SPEAKER_01I agree completely. Just take one step. I'm all about taking action, right? You know, I always tell everybody this isn't just a podcast, but my goal is to create a community, and we've referred to that quite a bit. You know, I want to make sure everybody that's moving through cancer um feels supported, that they have the clarity they need, the education they need, the support they need, and the information to make those difficult decisions, you know, and that's really tough. We want to fill their soul too with hope. And so I want to make sure everybody comes together collectively. I want to thank you so much for being here. You've been amazing, gracious with your time. Um, and you've also broken down so much critical, difficult, maybe scientific information in a way that we can understand it. So thank you very much to you.
SPEAKER_00Thank you for having me. This is always it's always wonderful talking with you, Lisa.
SPEAKER_01Awesome. Well, everybody, until next time, you know, let's come together collectively. Let's keep learning, let's keep supporting the critical research and doing whatever we have to to lean in. And you guys, let's keep moving hope forward.