Prof. Yelena Janjigian’s Inspiring Path in GI Oncology | OncoDaily

In this episode of OncoDaily, Prof. Yelena Janjigian, a renowned GI oncology expert from Weill Cornell and Memorial Sloan Kettering Cancer Center, joins host Ravi Karra to discuss her inspiring career and groundbreaking work in esophageal and gastric cancers.

From her journey from Azerbaijan to becoming a leader in oncology, Prof. Janjigian shares her dedication to advancing treatments that offer new hope in GI cancers. She delves into recent developments in immunotherapy, targeted therapies, and promising research in pancreatic cancer, particularly RAS targeting and cancer vaccines. Prof. Janjigian also emphasizes the potential for biomarkers and immunotherapies to improve long-term survival in GI oncology. An active ASCO and ESMO member, she highlights the importance of mentorship and fostering the next generation of oncology experts.

Yelena Janjigian is the Chief of Gastrointestinal Oncology at the Memorial Sloan Kettering Cancer Center in New York. She serves on the Steering Committee of the Giants of Cancer Care and is a member of the International Gastric Cancer Association Council. She is on the Editorial Board of OncoDaily. Her research and clinical practice improve treatment outcomes for GI malignancies. As an expert in esophageal and stomach cancers, she has led studies that set the standard of care.

Dr. Ravi Karra, Vice President of Oncology at Advanced Clinical, is highly experienced in brain tumors, melanoma, and head and neck cancers, with over 20 years in academia, pharma, and CROs. He has led clinical trial strategies for various cancers, including rare types like glioblastoma and uveal melanoma, utilizing translational research and biomarkers. Dr. Karra has extensive experience with regulatory bodies such as the FDA and EMA, contributing to multiple successful drug launches.

Ravi Karra: Good day, everyone, and welcome to today’s edition of Onco Influencers. I am your host, Ravi Kara, an editor with Onco Daily. We are excited to have Dr. Yelena Janjigian with us today. Dr. Janjigian is a professor of medicine at Will Cornell Medical College, New York, USA. She is the head of gastrointestinal oncology at the prestigious Memorial Sloan Kettering Cancer Center, New York, US. Yelena obtained her medical degree from New York University School of Medicine. She also trained in internal medicine from New York University School of Medicine. She completed her hemato-oncology fellowship from Memorial Sloan Kettering Cancer Center.

She is a very well-recognized key opinion leader across the globe in gastrointestinal cancers, specifically esophageal and gastric cancers, and as an investigator has led and participated to multiple practice-changing clinical trials in these tumor types with targeted therapies and immunotherapies. Elina, we are very glad to have you today. Thanks for your time.

Yelena Janjigian: Oh, Ravi, thank you for the opportunity and, of course, to you and Onco Daily for everything that you do for the education and advancement of our important advancements in gastric and esophageal cancer, but also for all tumor types. So thank you for the opportunity.

Ravi Karra: Thank you. I wanted to start off by asking a personal question to get to know you. Can you tell us a bit more about yourself?
Where are you from? Where did you grow up?

Yelena Janjigian: Of course, yes, of course. Well, now I identify as a New Yorker. I’ve lived in New York for the longest time out of all the places I’ve lived in my life, but I have moved around quite a bit, especially at the beginning of my life.

I was born in Baku, Azerbaijan and lived there till my teens, and then subsequently, because of the Armenian persecution and the war with Azerbaijan, we had to leave and to apply for a refugee status, and so we lived in Russia for a few years, so we moved from Baku, Azerbaijan to Rostov in Russia, which is a relatively big city on a big river, a well-known city in Russia. And then of all places after that, we moved to California, San Diego, because that’s where our sponsors were, their International Rescue Committee, their office in San Diego, California sponsored us as Armenian refugees, us, me and my family.

And then from California, from sunny California, which of course I loved, I moved to New York to pursue school and my education in medical school and so forth. And although my plans were to leave New York, as you probably heard this from many New Yorkers, once you live in New York, you can’t live anywhere else. So we now settled here and I’m a true New Yorker and love living in this beautiful dynamic city where you can really see people from all cultures and all backgrounds, and it’s a melting pot, true melting pot of the world.

Ravi Karra: Well, what an inspiring journey, I’m truly humbled by it. Why did you choose medicine and especially oncology to specialize?

Yelena Janjigian: Of course, oncology really attracted me by its unmet need and the science of it and how you really, to be a good oncologist and to be an excellent physician scientist in that field, I think it’s a perfect balance of need to always problem solve and not to be, you’re never comfortable, you’re always advancing and the science part of it.

And basically in oncology, we don’t read books, we read abstracts and papers and if something is in the textbook, it’s already outdated. So everything is so cutting edge and new and moving forward at a rapid pace, which I always was attracted to, especially once I’ve spent even just one week at Memorial Sloan Kettering as a house officer training. But the other part of it, and I think it in some ways attracted me even more, is the compassion that you need and the resilience that you need to be there for your patients.

And I remember when I told my parents, my mom, that I wanted to be an oncologist, she was so surprised because, and I think people ask me this at dinner parties all the time and cocktail parties as to why would you be an oncologist? It’s such a demanding and sad profession.

And I think that’s part of it, what attracted me, that you need to be compassionate, you need to be resilient because these patients otherwise have really very little to go by other than what you can do for them and how you can make them feel while you’re trying to help them. And that’s what attracted me. What attracted me to medicine? I think it’s probably similar to many of us as immigrants and as first-generation. It’s opportunity and it’s the dream that my mom, for example, had to become a physician. She wanted to be a physician all her life, but of course, living in Azerbaijan as a minority Armenian, you weren’t allowed to go to med school.

So I was always good at science. I was a good student. And so I went down that path as an opportunity. And then of course, I fell in love with it. And again, the compassion part of it and the challenge part of it is what really attracted me.

Ravi Karra: Great, great. Please tell us more about your current role and especially the tumor types that you treat and you research on.

Yelena Janjigian: So similar to my career in medicine and sort of getting into medicine by moving around, I moved around within the field of oncology quite a bit when I first started as a researcher interested in oncology. Actually, a lot of the work that I did was in liquid tumors, treatment-related myelodysplastic syndrome. And that’s what I thought I was going to focus on when I went into fellowship. so, in residency, I did a lot of TMDS work. And then while in oncology, I really pivoted as a fellow to lung cancer because I was very interested in the never-smoker’s lung cancer. And this was during that period is when a lot of the EGFR mutations were discovered.

And it was very nice to be part of the team with Will Powell, Vince Miller, and others at MSK that were at the forefront making some of these observations and discoveries that led to the characterization of acquired resistance with T790M mutations and lung cancer. Some of our trials that initially showed response to dual EGFR blockade in those patients and so forth.

And then when I was applying for jobs as junior early career investigator, it was an opportunity again in GI that presented to me the priority was to really stay at MSK because it was a unique place where you could get really a lot of research done quickly and difficult to answer questions quickly because of the support in the clinical trial portfolio and the translational opportunities and lab-based research that was going on. So, I pivoted to GI because that’s where the opportunity was and particularly since the HER2 story was really developing in gastric cancer.

And that was something I knew about EGFR receptor superfamily, how to study acquired resistance, how to characterize tumors that are oncogene addicted. And so I pivoted to that as an opportunity and stayed on GI and have never regretted it. It’s been an amazing opportunity as a scientist, as a physician, huge challenge, obviously GI tumors in particular.

I started my work with esophageal and gastric cancer and because we had some successes and challenges, but overall, how we overcome these challenges and grow is really what defines you as an investigator. And six years ago, or so I was given an opportunity to head the service and become the service chief, which was obviously a huge leap forward as a physician, a leader for me. And it was a great challenge again.

And I’ve really enjoyed that part of academic medicine, growing next generation of researchers, faculty, inspiring them to do more science-based investigation and translational work. And we’ve grown the service. I’ve grown the service tremendously since taking over because there’s this demand and also desire to really focus on GI tumors.

There’s an increase in incidence of all GI tumors, starting from the esophagus going down to the colorectal cancer and pancreas cancer. And so really we’re hiring better, brighter, more sort of innovative investigators than we’ve ever seen. And it’s really great to see all these, this enthusiasm and energy and talent going into GI space. And I’m there to help them grow and develop. So switching to GI has been a huge, really, opportunity for growth for me and others in the field.

Ravi Karra: Okay. Speaking about innovations, what is the latest innovation in gastric cancer with respect to number one, advanced setting, newly diagnosed advanced setting, and number two, in the recurrent metastatic setting?

Yelena Janjigian: Right. So I think a lot of the development in gastric cancer has really been made in characterization of different subsets of tumors. We know that it’s a rare disease in the United States, but globally it’s a very common problem with over a million cases diagnosed each year.

And the type of gastric cancer that’s declining in incidence is more your traditional, perhaps H. pylori or intestinal type gastric cancer, but the G-junction gastroesophageal junction tumors are increasing and rapidly in the United States. It’s one of the most, the fastest increasing in incidence of cancers. and it’s quite alarming. I think most of the development we’ve made was with characterization of the difference in these subsets, the molecular subtypes and how we can target them better and proving that immunotherapy works in these diseases.

We can improve survival. and for the first time, there’s long-term survival from patients with advanced metastatic tumors, where most of our patients present with metastatic disease. So, they need, so that we changed the definition of cure where you can live with this disease and continue to enjoy your life and stay on therapy that’s tolerable and offers you long-term survival.

So, there’s immunotherapy approval, there’s targeted agents’ approval, targeting both HER2, for example, and also Claudin inhibitors. So, there’s been over the last five years or so been major, major breakthroughs in metastatic disease. And now we’re working on bringing those breakthroughs to early-stage disease. And in some sets, we’ve been successful to do that, particularly for MSI, microsatellite and stable gastric and esophageal adenocarcinoma, also increasingly in HER2 positive disease. And there’s been some positive data in immunotherapy related treatments in early-stage disease. We’re waiting for confirmatory long-term survival data to come through.

So, I think this wave of breakthroughs over the last five to eight years has been focused on immunotherapy on characterizing biomarker subsets. and what we’re focused on next, particularly my group, and we formed a gastroesophageal therapeutic accelerator at Memorial Sloan Kettering to help bring collaborations and different data from different centers in US, Asia, Europe, Latin America, and from investigators worldwide to focus really on the undruggable subsets of these tumors.

Because a substantial subset, I would say more than 50% of those tumors don’t have a specific oncogene addicted profile that we can focus on right at this moment with targeted agents. And really the next wave of breakthroughs will need to be in that subset of cancers.

Ravi Karra: Okay. Thank you. Is it fair to say that immunotherapies, when they work, they really work and help the patients in the long-term, but do we know upfront which patients are going to respond?

Yelena Janjigian: That’s a great question. Yes. There’s approximately a quarter of our patients, 25% of patients have a long-term outstanding response to immunotherapy and survival.

Who those patients are, we probably know maybe 10% of them, who they are. And I can tell you, usually they’re high tumor mutation burden or microsatellite and stable, or perhaps have high level of HER2 and PD-L1 overexpression. But there is a subset of patients who we don’t know why they have such an amazing response. and it could be both host and tumor immune factors contributing to it.

And that’s where the uncertainty comes in, because when patients come in, they want that reassurance. They want to know that they’re going to be long-term survivors.
And we offer people hope, but who those patients are, we can’t know for certain because we can predict, but not with 100% certainty.

Ravi Karra: Okay. Jumping to a different tumor type, pancreatic cancer has been pretty resistant to any sort of innovation. So what is the message for the patients and investigators and the physician community out there? What can they look forward to with respect to pancreatic cancer?

Yelena Janjigian: Well, the message to the patients, the community and the researchers is the same. Keep going. I think we’re very close. I think pancreas has been one of those tumors where beyond chemotherapy, not a lot of drugs have worked historically, but there are breakthroughs coming.

And I think part of it is because of foundations like Glass Garden Foundation and others where a large attention has been drawn to this historically difficult to treat tumor. and there’s been a lot of research and funding going into the effort, including the vaccine, prevention vaccine, and also postoperative vaccines to help reduce risk of recurrence. That’s what our center is really focused on.

And also, therapeutics. So of course, it’s uniformly RAS mutant disease. and so improving RAS targeting, which has been in multiple iterations with different companies. Once there is one trial showing proof of principle, big pharma, biotechs, other philanthropy foundations are directing a lot of effort toward this disease. So, I think it’s the next one for a major breakthrough.

Ravi Karra: Thank you. That’s very heartening to know. You are a very active participant and member of several associations, most notably the ASCO and ESMO.
Can you outline broadly how you contribute to these societies? Are you a part of any committees and so on?

Yelena Janjigian: Yes, absolutely. It’s really, ASCO and ESMO are important vehicles for us to disseminate our research and to engage the next generation of talent. Whenever I’m given an opportunity to either present or host a seminar or lead a committee, this is what my goal is. Because I know that in my lifetime as an oncologist, I am unlikely to solve every problem. And so, I need to make sure that I leave behind a legacy of people like me or people who are exponentially better, smarter, more driven, more persistent than me. And that’s what these societies let us do.

So, I’m involved with several committees and also some of them are confidential because they haven’t been announced yet, but visibility with these committees is important. And sometimes it’s time consuming and challenging, but you are making a big difference because of that piece. You’re inspiring the next generation and not any less important, you’re also disseminating a message of research and a community of patients, caregivers, and clinicians who are in the in-clinic day-to-day.

They may not have the outlet of creativity that I have the privilege of having, which is research. And they also may not be sub-specialized. So, they’re not treating one particular disease, they’re treating all the cancers. So, to them, they rely on these educational sessions to understand how an expert like me, for example, in gastric cancer approaches the disease. Yesterday, I saw 33 patients with the same or similar type of cancer, gastroesophageal cancer.

So to me, these decisions are so nuanced that teaching someone in the community who may not see this disease very common, especially since it’s a rare subset of cancers, to allow that the patients who are getting care outside of a tertiary cancer center get to get access to the advances that we need as researchers in a place like Memorial Sloan Kettering is the reason why I stay involved with these societies and I continue to further their mission ultimately to improve patient care.

Ravi Karra: Excellent. Thank you. Being a physician scientist and doing academic research as well as participating to industry-led clinical trials, is there a particular tumor type within the gastrointestinal oncology part where you think, my God, why is no one taking a look at this?

Why is no one researching this tumor? Is there a particular tumor that you think along those lines?

Yelena Janjigian: Well, I think for a long time, it’s been the case for gastric and esophageal adenocarcinoma. I remember as faculty, junior faculty, trying to get investigative initiated trial concepts approved and based on idea that I had or basic science paper that I came across that I said this pathway or this biology would really apply to our patients because of X, Y, and Z.

And I think in gastric cancer and esophageal cancer, what lacked historically is the models of the disease because for biologic experiments preclinically, you really need a good transgenic model or other models to mimic the biology so that you can demonstrate efficacy or importance of a certain pathway. And I think slowly by generating patient-derived xenografts, organoids, but also models of the cancer in the lab, we’ve been able to break through that barrier.

And also, by doing studies, positive studies that the disease responded. So, you know, I think in gastric and esophageal, we can continue to improve on that. And then there are subsets of disease such as peritoneal disease, peritoneal carcinomatosis, where there’s nothing going on to improve outcome because peritoneal disease often fails all standard therapy. So, I think there’s still a lot to do in gastric. But, you know, certainly these niche subsets of cancers are where the opportunity is because if you show any positive signal, it really goes a huge way for a trial.

Ravi Karra: Thank you. Final, not a question, but a general, what would be your advice to budding oncologists who would like to specialize in gastrointestinal oncology? What would be your advice and message to them?

Yelena Janjigian: I think the advice and message is if you start a project, finish it, see it to a conclusion and try to learn as much as you can early on before your clinical administrative and other research responsibilities get, you know, too broad, learn as much as you can of skills that you could contribute to a team, some unique skillset.

For example, you know, if you have opportunity to go to a lab meeting or even be in the lab for one or two years as a trainee, even if you say to yourself, I will never have my own big lab or I don’t want to be a lab PI, still take an opportunity and learn skills and perspective that you would not get later on in life because these type of learning just for the sake of learning and understanding certain hard processes will give you an enormous advantage when you’re seeing patients in clinic, when you’re making observations, when you’re trying to come up with the next big thing.

And I think, you know, all of us need to be more daring, take risks and go for really big discoveries and not just incremental changes.
I challenge myself to do that every day and it’s sometimes difficult because, you know, these cancers are very challenging, but I think if we all challenge each other, you know, we will just get more done.

Ravi Karra: Thank you. On that note, thanks a lot for your time. It was very inspiring to hear your story from Azerbaijan to the U.S. and now as an international recognized key opinion leader in gastrointestinal oncology, we are very thankful for your time.

Yelena Janjigian: Thank you so much. It was a great, great questions and thanks for the opportunity.

Ravi Karra: Thank you.

Yelena Janjigian: Bye.