Women in Cancer: Meet Three Trailblazers at MSK

Dr. Diane Reidy-Lagunes:

Many are familiar with the names James Watson and Francis Crick for being credited with the discovery of DNA. However, another crucial member of the team is lesser known: a woman named Rosalind Franklin. It's a classic case of women's contributions to science being diminished and overlooked in history. In the decades since, we've come a long way, and although we aren't where we want to be yet, today's trailblazing guests are leading the way. In this episode, you all – our wonderful listeners – will hear fascinating and brilliant women scientists talk candidly about their pioneering work, as well as the pressures they feel, and the reason philanthropy is so critical to support their breakthrough research that will save lives. Let's talk about it.

Hello, I'm Dr. Diane Reidy-Lagunes from Memorial Sloan Kettering Cancer Center and welcome to Cancer Straight Talk. We're bringing together national experts and patients finding these diseases to have evidence-based conversations. Our mission is to educate and empower you and your family members to make the right decisions and live happier and healthier lives. For more information on the topics discussed here, or to send us your questions, please visit us at mskcc.org/podcast.

Our guests today are three remarkable women who are making an impact on the world of science and oncology. Trailblazers like this are what we call "women who curie," coined after Marie Curie, our most famous female scientist. We are joined by Dr. Karuna Ganesh, a medical oncologist and physician scientist specializing in colorectal cancer and models called organoids; and Dr. Chrysothemis Brown, a pediatrician and physician scientist specializing in immune regulation, which refers to how the immune system is controlled and coordinates its responses to threats. Both Dr. Ganesh and Dr. Brown are advancing cancer research forward around the world from right here in their very own laboratories at MSK. We are also tremendously honored to be joined by the esteemed Marie-Josée Kravis, MSK's Board of Trustees Vice Chair. Her philanthropy has focused on the arts, health and medicine, and education. She will share her insights and why she's so deeply invested in science and cancer discovery.

Thank you all ladies for being here and welcome to the show. So Chrys, let's start off. Can you talk to us about what exciting science you're working on now?

Dr. Chrysothemis Brown:

So in the lab, you mentioned that we work on immune regulation and what that is exactly is deciding how the immune system decides what to attack. I think everybody knows that the immune system attacks viruses and bacteria, and that's what protects us from infection. But the immune system also plays an equally important role in preventing your immune system from attacking things which are considered to be safe or useful to us. We have lots of bacteria. We're colonized with bacteria on our skin and in our gut, but we don't attack those bacteria and we also don't attack, for example, things like the food that we eat. So the immune system has come up with these pathways of immune tolerance to protect us so that we can have these kinds of healthy relationships with beneficial organisms.

We're trying to study how the immune system discriminates between these two things, deciding when to attack and when to kind of turn things off. Of course, that turns out to be very relevant in cancer because what we’ve found is that the immune system could attack cancer because it is foreign, but often it doesn't. So we're trying to understand what the switches are that would turn the immune system on and off.

Dr. Diane Reidy-Lagunes:

Amazing. And do you do that with cell models or with patient samples or a little bit of both?

Dr. Chrysothemis Brown:

A little bit of both. We do a lot of human work. We do a lot of work in animal models trying to model the immune responses against certain, bacteria or certain viruses, and then of course food as well as your sort of healthy bacteria. And then of course we do a lot of modeling of what happens during tumor development.

Dr. Diane Reidy-Lagunes:

Karuna and I both take care of patients with colorectal cancer and there's been tremendous work, as you know best, on the whole microbiome and bacteria and how that might contribute to colorectal cancer. Do you have any insights there?

Dr. Chrysothemis Brown:

Yes, and Karuna and I are actually working very closely on a project related to this. What we’ve found is that some of the clues actually lie in studying the immune system of babies or infants, which seems a bit counterintuitive, but this is actually when you first encounter your microbiome. It turns out that the immune system is exquisitely well-trained to develop a tolerance to the microbiota during this early life window. So we're studying some of the immune cells that actually underlie what we call this “window of opportunity” for developing immune tolerance.

Once you understand how the immune system regulates its relationships with the microbiome, then you can start to intervene to manipulate that process, for example, during cancer. We know that actually targeting the microbiota has turned out to have very powerful effects in many different cancers. But of course, colorectal cancer is a key sort of niche for studying because that's where most of your gut bacteria is.

Dr. Diane Reidy-Lagunes:

It's fascinating and something that, given the young onset of colorectal cancer that we know is happening in an alarming rate, I think that type of work can really make a tremendous difference in understanding the biology and the why. Karuna, can you share how your work dovetails to not only this type of work but also the pioneering work that you're doing in the lab?

Dr. Karuna Ganesh:

Thank you so much, Diane. So my lab studies metastasis and that's because I'm a colorectal oncologist and when my patients have disease that's only restricted to the organ where it started, we can largely cure cancer, which is amazing when you think about it. But once these cancers have learned to spread or metastasize to other organs from the one that they started off in, this somehow switches from being something you can completely cure to something you can never cure. So I've really always been really struck by this, and very curious to understand why is it that the genie now escapes from the bottle, and how can we put the genie back in the bottle? How can we cure these metastatic cancers, which are the main reason why people die of cancer?

So in my lab, to study this process of metastasis, we develop what are known as organoids, which are really just pieces of tissue that we collect from the patient's tumors, both from the primary tumors that don't kill and the metastatic tumors that do kill. We've learned how to grow them in these special three-dimensional balls, which are called organoids. These are really powerful because we can generate them from individual patients. We can see how the cancer cells change as they turn from the primary tumor into the metastasis states, and we can study what allows these cells to become so adaptable and stress resistant that they resist chemotherapies and eventually kill people. Of course there are changes that are happening in the cancer cells themselves which we have spent a lot of time studying, but increasingly we're becoming really interested in what's changing in the environment: the micro-environment – so how these cancer cells talk to the immune cells – and also the macro environment – the gut microbiome that we were talking about, what we eat, how that affects the hormones in our bodies, and how is all of that coming together to change how the cancer cells behave and how they interact with other cells around them.

Dr. Diane Reidy-Lagunes:

It's absolutely fascinating. Just to reiterate what you said: cancer is a population of cells, so that metastasis may be in a different environment when it gets to the liver versus the lung versus the primary tumor. Is that correct in thinking of it that way?

Dr. Karuna Ganesh:

Yeah, absolutely. And you can think of it as sort of two things: Are the cancer cells themselves changing as they learn to spread to distant organs? And indeed, recently we've discovered that that is indeed the case. So we can take cells from a primary colon tumor or cells that have metastasized to the liver from the same patient, and we find that they behave in really different ways. The primary tumor cells only know how to behave sort of like the colon, which is where they started off. But the metastasis cells we found are really adaptable if you give them different growth conditions. If you give different treatments, they're able to really quickly change the program of genes that they turn on and off to adapt. And so what we are really interested in trying to see is: how do the cancer cells change, and how do they respond to the microenvironment? How do those two things come together, and how can we disrupt those circuits to kill cancer?

Dr. Diane Reidy-Lagunes:

This is big science, and we would say sort of high risk in some of the work that you're doing, and I think all of us know that without philanthropy, it absolutely could never be performed. So Chrys or Karuna, could you share with us how philanthropy has allowed you to push the needle on some of these new developments that you're working on?

Dr. Chrysothemis Brown:

I think one of the most amazing things for me as a new investigator – I started my lab three years ago – is the scope of the work that we've been able to address and some of the questions that we've been able to go after. You know, typically an investigator at the earlier stage of their training, whilst they might have all of these ideas about things that they want to pursue, they don't normally get the money that would allow them to address the questions on such a grand scale.

What we appreciate in science is that the best ideas can come from any level. Any member of my lab can have the best ideas. They can be the most junior person. They can be the research technician. I think philanthropy has really enabled our lab to go after things that before you’d have to prove that you've worked in a field for 20 or 30 years. So now you can go after some of the most exciting questions. And I think sometimes that's where the discoveries come from, not the sort of incremental discoveries, but the ones that really change a field or change our perspective on something. So I think that the pace of science that happens through philanthropic funding is absolutely incredible.

Dr. Karuna Ganesh:

Absolutely, I second that. And the way federal funding, which has historically been the main source of science funding, has worked is that you need a lot of preliminary data and often you have to ask questions that are not very risky. You have to show that you're going to achieve your goals. And the highest risk, highest reward, most exciting ideas that are really pathbreaking often aren't supported by preliminary data. So we really need philanthropic support to seed some of those early experiments that allow us to be competitive eventually for getting funding.

And on another level, science is not just a set of experiments. Science is done by scientists and teams of people working together, often young people who are trainees. People need motivation and team building activities. On that level I'm particularly grateful to Mrs. Kravis for her generous support of what we call the “fun fund,” which has funded, since the pandemic and beyond, numerous sorts of small-scale outings so that we can go and celebrate and do team building exercises, things that federal funding is not designed to support. You're given money to execute specific experiments, not to go on team building exercises, but all of that of course contributes to the quality and the excitement of the day-to-day science.

Dr. Diane Reidy-Lagunes:

And the innovation, right? Just the excitement of thinking about these ideas that, in today's crazy world, we don't just get a chance to think about some of the wonderful thoughts and opportunities to advance the field. Marie-Josée, you have given so much to so many, but why in particular is cancer research and oncology so important to you?

Marie-Josée Kravis:

I think medical research generally is important to my husband and myself. What I think is unique at MSK is this combination of foundational science or basic science, translational, and of course, patient care. For us, it seemed that when we were looking at where the gaps were in terms of support, it's harder to raise funds for basic science, curiosity-based science that's not directly related to developing a therapy or a product, but it's really unleashing curiosity and investigation. And so we thought that's probably where we could have the most impact, by supporting that curiosity-based basic science.

You were speaking about immunotherapy, for example, but it's hard to apply immunotherapy if you don't understand how the immune system works. And so basic science allows you to dig deeper and deeper and deeper. For us to be able to give investigators – and you've just heard two very high-quality investigators – the ability to let their curiosity and their skills investigate with more freedom, I think is really important.

Dr. Diane Reidy-Lagunes:

Absolutely. I think as a female philanthropist, your viewpoint, not only because you understand the science so clearly and you have a passion to want to understand, but you're also bringing something very special to the table. So what are some of the things that you think about in terms of how you might want to support these scientists and cultivating an environment that not just allows that curiosity to spread and also allows them the time to think about these important issues?

Marie-Josée Kravis:

I think giving them a little bit more respite in terms of raising money and raising funds and directing their efforts, more to actually conducting science, is important. You mentioned women, and I think that women in science have been somewhat overlooked, so I think we need to give women more recognition. They're really powerful role models for younger women who envisage studying science and medicine. I think that's very important, to recognize real achievements and to encourage new ones.

Dr. Diane Reidy-Lagunes:

Along those lines, let's talk about the importance of mentorship because Karuna and Chrys, you're both trailblazers. You're trying to revolutionize the way we think about cancer oncology and research, but I'm sure that's not without challenges. So can you share with us a little bit about your own community, how you might find that support and the importance of mentorship for you?

Dr. Chrysothemis Brown:

Mentorship has been fundamental to my career decisions. If I think about how I ended up going into certain medical specialties, how I went into certain scientific disciplines, how I ended up moving from certain countries, it was always inspired by a particular person. And the inspiration can obviously come from people who aren't your direct mentors, but I think your mentors give you something else. They give you the possibility to believe that you can achieve what you're going after, and sometimes they can also make you realize that your vision can be even bigger than you had imagined and that you should go for it.

So I think mentorship is absolutely fundamental, but I think it's so important in sciences because there's so much failure baked into what we do, which we often don't talk about, that 90% of what you do is kind of set up to fail and that can become really demoralizing. So I think you need someone in your corner who's going to be your champion to make you realize that it's normal and you have to keep pushing on through, and that you will still succeed at what you are going after.

Some of what has been put in place at MSK – for example, the fellowships that Marie-Josée has supported for women in science – have been absolutely critical for that because it means that we have junior graduate students in the lab who can be part of that celebration from a really early stage of their career. Often you have to wait a long time before you get recognition for what you do. I think being able to pass that on is really important.

Dr. Karuna Ganesh:

I think you said that beautifully. I don't think I have a lot to add there, but I will say that I think often people look for everything from one mentor, to be able to teach you everything about life science, everything. And often, I’ve found that it's really useful to build a community of mentors, understanding that you want to learn from the best, the most valuable thing, that each person has to teach you. Your life and your career trajectory may not be the same as the next persons, but you can learn from everyone around you pieces of the puzzle and put them together the way you want to build your life and your career.

And again, the fellowship programs like The Marie-Josée Kravis Fellowship and others like it have really helped to create those kinds of communities at different levels of trainees, and also for junior women faculty. More than ever I feel like I need mentorship at this stage in my career where we are balancing so many things: medicine and lab and childcare, all of these things.

Dr. Diane Reidy-Lagunes:

Yes, absolutely. And Marie-Josée, talk to us a little bit about KravisWISE, which is the Marie-Josée Kravis Women in Science Endeavor, that provides funding for professional development and mentorship.

Marie-Josée Kravis:

It came as a wonderful gift from Henry, from my husband. I think he asked me what I wanted for a birthday, and I felt that we have enough things. Why not do something that's meaningful for someone else? It's something that lasts. So this is how this gift was made in my honor for a special occasion, but also for special people. And the idea was to provide fellowships, but it was also to provide support for investigators who need to travel but have children at home or need financial support to either pay for their travel expenses, something that isn't covered either by MSK or by grants and so on. So it was really an effort to strengthen and to support the work of women at MSK in the scientific endeavor.

Dr. Diane Reidy-Lagunes:

I just think that's such an extraordinary gift. I didn't realize that it was from your husband. It's just so beautiful. We need men supporting us, so the fact that you chose that and it was his gift is even better of a story.

Marie-Josée Kravis:

And it's a gift that keeps on giving.

Dr. Diane Reidy-Lagunes:

Amen. Any advice from the three of you for young women considering a career in research? I listen to you and how you talk, and I have to be honest, like, how do I inspire my own daughter to think creatively and innovatively about science? You know the motto of, "If you can't see it, you can't be it." So how do we get our young girls and bright women to think about a career in science and think that it can be done in a successful way?

Dr. Chrysothemis Brown:

It's interesting, I am involved with the graduate school recruitment at MSK, and I think we have more female applicants than we have men. I don't think that the issue is at the junior level, really inspiring scientists. I do think outreach is very important so that young students get to hear stories and see female scientists. I think the problem gets harder as you go further through your career. I think it's telling that so few of my mentors have been female. Female representation is definitely lacking at the more senior level. So I think we definitely have a problem with drop off in terms of, we have really bright female graduate students, and we have really bright female postdocs, but we don't necessarily have equal representation at the more senior level. I think that's a real challenge,

Dr. Karuna Ganesh:

I agree. I think we really need to do better at getting women from the junior faculty stage to leadership. I think we are doing better overall, but there's still work to be done. I think growing up through science, most of my mentors like Chrsy's were also male, and it didn't really bother me. Many times, not from the mentors but from other people, I would hear that, “Oh, you shouldn't do this,” or “You shouldn't make this career move because it's too risky,” and I basically just ignored everyone and just kept doing what I wanted to do.

But now that I'm on the other side as a P.I., I'm struck by how many women come to me, either by reading articles that I've written or through the graduate schools and so on, who want to work in my lab in part because I'm a minority woman and they feel excited to see somebody who looks like me in my role. Maybe that wasn't something I was cognizant of when I was looking for mentors and role models, but it's clearly something that a lot of people want and need and benefit from, right? So I think we need more of us, more women, doing what we are doing and getting out there and telling people that, yes, you can do it. If you want to be a scientist, you can do it.

Dr. Diane Reidy-Lagunes:

Absolutely. I think that's so critical. We talked earlier about how we all have failures, but we keep going and we hold tight to those positive wins that can really leap forward the science in a way that we never imagined. And so that was terrific advice, Karuna, about the noise and trying to avoid that and trying to keep going is hard but important. Chrys or Marie-Josée, anything else in terms of advice you might give to women that do feel like the challenges can be a bit much, and for various reasons they're just not succeeding in the way that they feel that they should be?

Marie-Josée Kravis:

I think you've hit the nail on the head in saying that it's oftentimes discouraging that 90% of your efforts are not fruitful. I don't want to call them failures because you learn from them, but I think that we tend to celebrate success readily. But that is normal and that's why science is complex. That's why you espouse this profession. That's why you keep on doing it.

To have more female role models is something that I certainly want to support much more aggressively. I’ve found that in every walk of life, people tend to hire themselves. They hire people who look like themselves, who act like themselves and so on. We have to break that and have a greater diversity of people so if they are hiring themselves, they're hiring a more diverse group. I think that those are two big, big challenges: supporting efforts that don't succeed and supporting a much more diverse population in science.

Dr. Diane Reidy-Lagunes:

Getting back to that science: what are you most excited about in terms of where the ball is going? What science are you excited to try to work on or see come to fruition?

Dr. Karuna Ganesh:

I'll step a little bit outside my normal things about metastasis and talk actually about immunotherapy. When patients have metastatic disease, I just told you that by and large, this is considered incurable. But in the last 10 or 15 years, through work done here at MSK, we now know that some of our patients with advanced metastatic disease can actually be cured by harnessing the power of the immune system to control these tumors and keep them back in check. That works amazingly well for some patients, but for many of our patients with the gastrointestinal cancers, colorectal cancers, pancreatic cancers and others, that has not proven to be the case so far.

But I'm really excited about what the future holds. I think we are really at the cusp of potentially being able to nail this. I think the more we can understand about how the immune system works at a really fundamental level – maybe Chrysy's going to solve this problem for us – and how tolerance develops – especially to these gut organs which are always at this interface with the outside world so the immune system has to be told to calm down and not attack those organs all the time – how do we break that tolerance and how do we get these cancers to respond? I think that's going to be really, really exciting.

Dr. Diane Reidy-Lagunes:

Chrysy, we're waiting. We're hoping for you to do that.

Dr. Chrysothemis Brown:

Yeah, I was going to follow up on that.

Dr. Diane Reidy-Lagunes:

Keep going, keep going!

Dr. Chrysothemis Brown:

I think that's the area we're so excited about. I think the discoveries that came out of MSK that have led to checkpoint therapy have kind of revolutionized treatment of cancer. It's an example of, as we said, having to go for high risk, high reward science. It took a long time for people to think that the breakthroughs in cancer were going to come from the immunology field, but I think that's really only the tip of the iceberg.

We have a couple of immune regulatory pathways that we've targeted that have turned out to be very successful in certain kinds of cancers, and now the question is, what about other cancers? One of the things that we think about a lot in the lab is children's cancer. So, for example, checkpoint therapy has really revolutionized adult cancer, but it's very rarely turned out to be successful in pediatric cancer, and so the question is, why not? I think what that's telling us is what we've known for a long time, is that the immune system of children is not the same as adults. So if you really want to start getting into precision therapy, you have to understand the immune system at the point where you are delivering your treatments. So that's something that we're very excited about in the lab, and we're hoping that as we start to understand more about how the immune system develops in early life, we can start to tailor some of our therapies.

Marie-Josée Kravis:

Well, that’s music to my ears because as you know, supporting immuno-oncology is one of our priorities right now as well as the ecosystem project, which will look at cancer in terms of the whole system, the healthy as well as the cancerous parts of the body. Cancer is a physiological disease, not just the genetic mutations. Understanding cancer as a physiological disease is a priority right now, and I'm glad to hear you say that.

Dr. Diane Reidy-Lagunes:

And going back to the philanthropy, just as an example of what the fruits of philanthropy have succeeded in accomplishing, it’s exactly what you said. The Kravis Center for Molecular Oncology, which was an idea, a big idea, a very expensive idea that you and Mr. Kravis supported, has become standard of care treatment in today's clinic. So every patient that I see in GI cancers are getting what we call molecular profiled to be able to understand the genetic mutations of that cancer to see if we have something either that we can target or that can share with us a better understanding of the biology of the cancer that I can share with the patient, if it's going to be a little bit more aggressive or not, based on what we understand. And so I think it's just such a beautiful example of a big, bold idea that is now part of the routine practice that we have in caring for our patients.

Marie-Josée Kravis:

Thank you.

Dr. Diane Reidy-Lagunes:

Karuna, Chrysy and Marie-Josée, thank you so much for all you represent and for joining us here today. I learned a tremendous amount from all of you.

Dr. Karuna Ganesh:

Thank you.

Dr. Chrysothemis Brown:

Thank you.

Marie-Josée Kravis:

Thank you.

Dr. Diane Reidy-Lagunes:

Thank you for listening to Cancer Straight Talk from Memorial Sloan Kettering Cancer Center. For more information or to send us your questions, please visit us at mskcc.org/podcast. Help others find this helpful resource by rating and reviewing it on Apple Podcasts or wherever you listen. Any products mentioned on this show are not official endorsements by Memorial Sloan Kettering. These episodes are for you but are not intended to be a medical substitute. Please remember to consult your doctor with any questions you have regarding medical conditions. I'm Dr. Diane Reidy-Lagunes. Onward and upward.