Transcription:
Innovative Breakthroughs in Cancer Care

Dr. John Leonard, MD (Host): Welcome to Weill Cornell Medicine CancerCast: Conversations About New Developments in Medicine, Cancer Care, and Research. I'm your host, Dr. John Leonard, and today's topic will be Innovative Breakthroughs in Cancer Care and Research. Today's guest is my good friend and colleague, Dr. David Nanus. Dr. Nanus is Chief of Hematology and Medical Oncology at Weill Cornell Medicine and New York Presbyterian Hospital. An international leader in the treatment of kidney, prostate, bladder, and testicular cancers, Dr. Nanus is actively involved in research initiatives to bring new therapies for patients. David, it's great to have you here today. Thanks for taking the time. 

Dr. David Nanus, MD (Guest): John, I just want to say thanks for having me on your inaugural podcast, and I look forward to its success in the coming months and years, and it's always a pleasure to sit down and talk with you.  

Dr. Leonard: So we're going to get into in a minute some of the new and exciting areas in cancer care, cancer research and treatment, but I know a number of the members of our audience are patients or family members. I mean why, just as we get into this, and I think getting access to some of these new technologies is one reason why patients should at least look into research. But what are some of the other reasons why patients from the patient perspective, somebody dealing with a serious illness, a cancer diagnosis; why should they either seek out participation in research or treatment at an academic center, and participation in studies? What are some of the key advantages there?

Dr. Nanus: So the first advantage I would say, which is often overlooked, is that there's many studies out there that show that patients who actually are in clinical trials get better care and better outcomes. Now I'm not talking about just that they live longer, I'm saying their ancillary care, their quality of life, their management of symptoms is actually better on a clinical trial. 

So there's a perception by patients, "Oh if I go on a trial, it's an experiment, it's going to be worse than standard of care. I'm only going to go on a trial at the very end when there's nothing left." That's actually incorrect. So for years we've shown that patients, if you do surveys of patients on studies that get the treatment arm, versus let's say a placebo arm, or the standard of care arm, they do better. They have a better experience with cancer.  when you go on a study you become part of that study. You have a team taking care of you, and you're informed, and you help with the decisions. 

And then finally there's the real personal benefit, which is hey, you get a new investigational agent. John took care of my sister-in-law with lymphoma. She went on a clinical trial, she's alive eight years later doing fantastic. You know, so that's the personal benefit, and then there's obviously the altruistic collective benefit of advancing science and helping other patients. It's not just only about you, it's about other patients you don't want to suffer like you and your family suffered, and it's about the patient and their family.

Dr. Leonard: So one of the things we wanted to do in this episode was kind of do a bit of a round robin of some of the hot areas in cancer care, and I think these are areas that are exciting, they're buzzwords, people read about them in the paper. Certainly a lot of research here going on, and at other centers around the country, and I would say that all of these areas are exciting, and they all have limitations. 

And so we're going to actually in future episodes go into a lot more depth on all of these areas, but I think it would be great- I mean you sit in a unique place where you're building programs here, you're leading aspects of our center, and where we're investing, where we're focusing some of our research efforts. So we're going to talk over the next few minutes about areas that people have heard about such as genomic profiling, precision medicine, immunotherapy, CAR-T cells, liquid biopsies, treatment resistance; all of these are kind of buzzwords that you can go to a medical meeting or a research meeting and spend the whole three or four days talking about. 

But let's just kind of in a rapid fire thing give people a flavor of kind of- we'll start with genomic profiling and precision medicine. Kind of briefly, what is that area? Why could that be great? And where are the limitations of that area as it stands right now? 

Dr. Nanus: I think that there is- this is probably one of the more exciting areas of medicine, and I'm going to make it very simple for patients. Really it was the site of origin. So to think about it, where the cancer began, that's how we define cancer. As technology advanced, as molecular biology advanced, as research advanced, we realized that we could analyze tumors by their DNA, their proteins, go in very deep, and we saw that it wasn't so much about where a cancer began, though that still is important, but- or the cell of origin, but really what is those genetic abnormalities that are in the cancer itself that can help define it? So one tumor that could arise in the lung, or the liver, or the stomach may have the same genetic abnormality. 

And some of those genetic abnormalities actually create vulnerabilities, or make the cancer a little bit weak to certain treatments. So if you say, "Well this is the abnormality that's making this cancer grow and spread, if I can find a drug or an intervention that targets that abnormality regardless of if it started in the lung, or the stomach, or the liver, maybe I can impact the patient." And that's really what this whole concept of genomic profiling and precision medicine is about. It's being precise, meaning that we're going to take your tumor, we're going to see and look at its abnormalities, and more importantly then we want to use targeted therapy to attack that tumor regardless of where it is. 

And we've been very successful. I mean, I have patients that have bladder cancer on breast cancer treatments that are alive and appear to be cured. Unfortunately there are some of these common abnormalities we still have not developed the drug that kills them. Like maybe you may have heard of RAS as an example, but that's coming. I'm confident with the continued research, we will be able to develop new drugs and do approaches that will kill these cancers.

So getting your tumor profiled, using that information to guide therapy, is really state of the art medicine that can only be done initially at major academic centers, not it can be done commercially, and that's really made a huge impact on how we care for our patients.

Dr. Leonard: And I think the greatest impact of this is yet to come. There was an interesting debate, I think at the AACR meeting not long ago, where giving examples of success, but also potential criticisms that it's really a limited number of patients in some areas where this has had an impact, but over time that should continue to grow. 

So I want to move now to another area that is really hot, and there are a lot of discussions around immunotherapy, and we have these immune checkpoint inhibitors, we have in a more- I don't want to say 'extreme' way, but perhaps an involved way, and patient specific way, the CAR-T cells. But tell us just kind of your sense of- in a big sense, why is immunotherapy such an important potential modality, and where does that stand in treating cancer? 

Dr. Nanus: So first, just to follow up on what we just said about genomic profiling, that's where you have a therapy that targets a specific abnormality of mutation, the cool thing about immunotherapy is it really doesn't matter, right? So if you have a tumor and immunotherapy is effective, it's regardless of what the genetic abnormalities are, and that's why some of the same drugs can be used in many different tumor types.

And actually the more mutations you have- studies are showing the more mutations you have, the more likely immunotherapy is going to work. And really what it does, is it unleashes your own immune system to fight the cancer. We've known for many years that tumors can turn off the immune system in the area of the tumor, so what these new drugs do is they turn back on the immune system and it attacks the tumor. Now that leads to some side effects potentially, because if your immune system is activated, it may attack you. Meaning so it could attack your liver, your lung, your joints, your skin, et cetera, though hopefully we're fairly good at controlling those side effects. 

So I think this is also one of the more exciting areas of cancer. I do believe it works, but not in enough patients, and that's one of the difficulties I think we as clinicians have, is some patients it works great, and if it works in you as an individual patient it can be a real home-run, and even a cure. But unfortunately, it still isn't working in a lot of patients, and this is where research and clinical trials come into play again, because now we're doing new types of immune therapy combinations, trying to figure out what's the best approach to really allow your immune system to attack your tumor. 

So this again is a very promising, really exciting area of treatment, and I've seen many patients benefit that I know years ago would not be alive today that are still alive and with their families, and everything is going extremely well for them. So it's something to continue to look forward to. I think it will continue to grow, and impact our patients.

Dr. Leonard: One of the areas more commonly explored and we now have a couple of drugs available, more in the hematologic malignancies, although they will be at least studied in solid tumors more, is the concept of CAR-T cells or chimeric antigen receptor T cells. This is an area we'll talk more about in the future, but it really involves taking from a patient their own T cells, which are immune cells that help fight infections, but then can be engineered in a laboratory to better target tumor cells, reinfused into the patient like a fancy transfusion, and then we can basically go throughout the patient's body, seek out the tumor cells, and develop an immune response against them. And so that's another area that has received a lot of attention we'll talk more about. We have approved drugs now in leukemia, and lymphoma, and a lot of research going on there. Some toxicities that you alluded to going on there as well. 

So you know, this is an exciting field and getting a lot of attention, but in general you also alluded to the toxicities of immunotherapy. Does this all speak to the importance of doing this in a systematic way and participating in studies rather than kind of willy nilly saying, "Well, you have a bad tumor. Let's try immunotherapy and see what happens." And maybe we'll get lucky, but often we won't. What's the approach there?

Dr. Leonard: So there is a lot of work going on in immunotherapy, we have some great examples of kind of miraculous or very heroic responses in people in difficult situations, but on the other hand there are lots of people who don't benefit or who haven't benefitted. I think the concept of is this something that should be given to people in a willy nilly sort of fashion, or is it much better obviously to think about it in clinical trials and in new rational approaches? What's your take on that? Because a lot of patients are asking about this, and when people face desperate situations, looking at this in a very logical fashion makes a lot of sense.

Dr. Nanus: I got an email this week from a patient specifically about CAR-T therapy, his father had a solid tumor, and I explained to him this is what we're seeing like you said in leukemia and lymphoma moving forward. These are very toxic, potentially toxic therapies with a really high upside, and should be done in an academic center, even a center that does bone marrow transplants, because the patients can be so sick from the treatment. 

That said, it's very exciting for the right patient. This is a road to cure, so I think we need to move forward. There's a lot of research going on and taking this concept of activating your T cells to fight many types of cancer. Oh, I do think in the future it will be limited regardless because of the expense and the side effects, but it is an exciting area, and more to come, and the only way we're going to move this forward is by patients agreeing to enroll in clinical studies. 

Dr. Leonard: So another area that has gotten some attention, and one you've been very involved with, particularly in prostate cancer, is the concept of liquid biopsies circulating tumor cells, circulating tumor DNA. Patients are familiar with the concept of having to get a biopsy when they're diagnosed, or maybe surgery when they're diagnosed, and then wanting to track what's going on with the tumor over time, and having to get repeated biopsies. The concept of not having to get surgery, and not having to get needle biopsies, and being able to track markers of the tumor in the patient's blood sounds very attractive. So tell us about your work in that area, and where you see that field going.

Dr. Nanus: So patients in general undergo a lot of different therapies through their life with cancer, from diagnosis to one treatment, they relapse, another treatment, and this can go on for years and years. And cancer cells in some way, if you can think of it like a bacteria. So you have a bacteria, you treat it with one antibiotic, what grows back is a little bit more resistant. You select with the antibiotic, then you give them another antibiotic, what grows back is even more resistant, and you have to define that resistance, and we actually do that, right? We take a culture of the bacteria, we go to the lab, we say, "Well this antibiotic used to work, now it doesn't work," and so forth. 

It's not so simple in cancer, in part because you would have to go and do invasive biopsies, you'd have to stick a needle somewhere, you'd have to try and hope that that's representative of the whole- of what's going on in the entire body. And obviously it happens over time, so it could be months later, you have to respond, the new treatment is getting worse, and now what's going on? Why is it resistant?

So we've moved more towards this concept of a liquid biopsy, meaning that can we draw a tube of blood and extract either circulating cancer cells that are released from the tumor that are floating in your circulation and analyze them, or more recently over the last few years, even just the DNA that comes from the tumor, we can differentiate DNA from a cancer cell because of mutations from DNA from the normal, and use that information to guide therapy and say, "Oh God, you have a new mutation."

In lung cancer, for instance, there's an FDA-approved test, patient goes on a treatment for lung cancer, with a certain type of lung cancer, they're doing fine, it's getting worse. You take a tube of blood, you say, "Oh, they have a new mutation in that gene that we were targeting. Now we're going to give them a new drug specifically for that gene." 

So that's a liquid biopsy. Historically you'd have to do a- try and get a real biopsy which has potential complications. So that's real advancement, and I guess the real advancement is just the ability to do this quickly over time and sequentially and continually guide your therapy.

So I think this whole idea of using blood tests to treat patients, to inquire about what's going on in the cancer is really also one of the really hot topics of today and it all speaks to technology. What we can do today is unbelievable, and there's companies, and research laboratories that are continually improving on this technology, and I think ultimately the vision of the future is we draw a tube of blood in a normal patient and say, "Wow, you have early stomach cancer based on this. We need to go look and try and find it." And I think that's what people are hoping in the future.

Dr. Leonard: So patients ask about this, and it sounds great. On the other hand you work on prostate cancer. So when we talk about sampling the blood for tumors, kind of what's the- does it make a difference? 

In terms of is it already making an impact? Yes. So we know that many tumor types have defects in their ability to repair DNA damage, okay? And they have proteins that normally repair DNA, and if they're not working well, if they're mutated, the patients develop cancer or their cancer can progress, we have drugs that will work in those patients who have DNA damage repair abnormalities. We can test that, and we can identify that in a liquid biopsy. So already today, information with liquid biopsy, a blood test can be used to guide therapy. I think it's only going to continue to improve and expand. 

Dr. Leonard: So that leads us to I think the last topic that we were going to get into today, and that is the concept of treatment resistance. Patients all the time, obviously they are diagnosed, they get a treatment, the treatment works, maybe it doesn't work, the disease comes back. What are some of the latest thoughts on treatment resistance? And obviously that's evolved from the standpoint of chemotherapy treatment resistance, and now some of the new targeted therapies with resistance to more targeted treatments, immunotherapies. In a big picture, what are some of the hot areas there and the current thinking in a general sense about resistance to treatment?

Dr. Nanus: So cancer cells evolve, and they evolve by making new mutations, new abnormalities, or trying to bypass different blocked pathways. Without getting too technical, this is normal. I mean you would expect an organism as highly developed as us would have a lot of pathways that are redundant or that are similar in order for us to survive adverse situations. Cancer cells take advantage of that and they say, "Oh you blocked this pathway with a drug? Oh, I'm going to take this side street to get there." The main highway is blocked, just like we do every day when we drive to work in New York. John and I both live in Westchester, we come to work, some days we have to go through Queens.

So cancer cells are very similar in their ability to do that. So research is discovering that. We say, "Oh wow, this worked and now it's not working. Why?" And we say, "Oh well they're taking a bypass road, or there's a new mutation." Well what if we start in the beginning and give two drugs and say, "We're going to block not only the main highway, but the other way to get there." And that can sometimes be more effective. 

So that's where research comes in, understanding resistance and sensitivity, right? So I mean just if you have a drug, and this is what's happened in the last few years, so we give a drug to patients with lung cancer, and it worked 5% of the time. We say, "This drug is not working," and we put it back on the shelf and move on. Now we say, "Well wait a second, if you have this mutation, this drug works 100% of the time. And gee, 5% of patients who have lung cancer have this mutation. So suddenly you say, "Okay I'm going to use this drug only in that patient population with that mutation," and it's a homerun. It works all the time.

So that's where this idea of treatment sensitivity, treatment resistance, guiding therapy based on that makes a big difference. And even in those patients, sometimes they develop resistance and then we say, "Oh well now we know why, let's develop a new drug." So it's not only understanding what the resistance mechanism is, but quickly coming up with a new strategy to combat that resistance so we can treat the cancer and kill the cancer.

Dr. Leonard: Well David, you know we've touched on a number of different topics today. For someone who might be a patient out there, or a family member of a patient who's trying to navigate cancer treatment, and obviously these very challenging diagnoses, as you guide patients, as you guide others dealing with cancer, what are the key messages for patients to think about as they are kind of navigating this system, being confronted with a diagnosis, that can help them avail themselves of some of these new advances to hopefully have a better outcome?

Dr. Nanus: First of all I recognize, as I know you do, that cancer is very scary. It's scary for patients, it's scary for patients' families, it's probably one of the biggest fears that everybody has. They feel a lump in their neck and say, "Oh my God, I'm dying of cancer." So we have to recognize that there's a lot of anxiety and patients need to understand that's normal, right? That's part of the process of cancer. It's not just getting a disease, getting a drug. 

And so patients need to be informed. They have to understand what their disease is, what the treatment options are, and enlist family members, I think advocacy is very important. I'm a big believer in advocacy and am involved in a lot of prostate advocacy. Patients and their families need to be empowered because not even every doctor in the community knows everything. If I'm a doctor taking care of ten different cancer types, it's not like coming to me- all I think about maybe is prostate cancer. I know a lot about prostate cancer. You wouldn't come to me if you had breast cancer because that's not what I do. In the community it's a little bit more difficult, so you have to understand the limitations, and there's like I said many great doctors out there, but sometimes you need to go to an expert and enlist your family and friends. 

I also think the misconception, as I said earlier, that clinical trials are for late stage patients. Clinical trials should be your first question. "Am I eligible for a clinical trial, Doctor? What is the standard of care? Is this going to cure me? Is there a possibility if I did something else?" Really what happens is once you go down a treatment pathway, sometimes you're not eligible for a trial because it's for a certain state of disease, a certain time in the treatment path that you can get on that study. 

And I think it's important that your voice be heard as a patient. I think doctors want to be with you, want to work with you. It's a team approach. It's not only the patient, it's the nurses, it's the social workers, it's the nutritionists, et cetera. So you as a patient need to not consider yourself a victim of cancer, which we all are if we're diagnosed with a cancer in some respects, but more of someone, "I have an illness." Frequently cancer today is a chronic illness. Don't walk out of here thinking you're dying. You're not dying, we're talking about living. Let's talk about how we're going to live, not how we're going to die. You're going to live for many, many years." There's always hope and optimism for the future.

Dr. Leonard: Well these are great messages I think, David, for people to take forward, and as I said earlier, I think we've covered some of the very exciting new areas and important areas in cancer care and research today. We're going to come back to many of these topics in future episodes, and I know, David, the program you lead here at Weill Cornell has active clinical in research activities in each of these areas. So there's a lot happening, and it's really exciting. I think we have a ways to go in some of these areas, but many of these new technologies and new approaches are even already benefiting patients today. 

So I want to thank Dr. David Nanus, Chief of Hematology and Medical Oncology at Weill Cornell Medicine and New York Presbyterian Hospital again for joining us today for the session, and we look forward to future discussions on many of these and other areas. I want to encourage our audience, that you can feel free to email us at CancerCast@med.cornell.edu. Again that's CancerCast@med.cornell.edu. You can send us questions, comments, topics you'd like to hear us cover more in depth in the future, and we'd be very happy to have your feedback. That's it today for CancerCast: Conversations About New Developments in Medicine, Cancer Care, and Research. I'm Dr. John Leonard, thank you very much for tuning in.