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The PancChat Podcast is a collaborative effort from Let’s Win Pancreatic Cancer and the Pancreatic Cancer Action Network (PanCAN), inspired by the long-running #PancChat Twitter/X chat.
Hosted by award-winning journalist Alisyn Camerota, each episode features conversations with leading researchers, clinicians, patients, and advocates who are shaping the future of pancreatic cancer care and research. Together, we deliver expert insights, personal journeys, and the latest breakthroughs—bridging the gap between science and lived experience.
Whether you’re a patient, caregiver, healthcare professional, or simply want to learn more, join us to connect, be inspired, and learn how you can help to accelerate progress in the fight against pancreatic cancer.
Julie Fleshman: Hi. I'm Julie Fleshman, president and CEO of PanCAN. In today's episode of PancChat, we are looking at where the field is heading and what's on the horizon.
From immunotherapy to early detection to new treatment combinations, researchers are working on approaches that could significantly improve patient outcomes.
Host Alisyn Camerota is joined by Dr. Andrew Ko, who shares his perspective on what's next in pancreatic cancer research.
Alisyn Camerota: We want to welcome our listeners to the PancChat podcast. I'm your host, Alisyn Camerota. We also want to thank our sponsor, Revolution Medicines. So today we're looking at the future of pancreatic cancer research — what's on the horizon and what breakthroughs could be coming our way?
Our guest, Dr. Andrew Ko, is here to help us understand where the field is headed. Dr. Ko is a professor of medicine and associate chief of hematology oncology at the University of California San Francisco. His clinical and research interests are in gastrointestinal cancer, with a particular focus on pancreatic cancer. He chairs the NCCN Pancreatic Cancer Guidelines Committee as well as the NCI Pancreatic Cancer Task Force. He is a PanCAN research grantee. Dr. Ko, thanks so much for being here.
Dr. Andrew Ko: Thank you. It's a pleasure to be here.
Alisyn Camerota: So let's start with something that is considered the holy grail of pancreatic cancer treatment, and that is vaccines. People talk about vaccines all the time. As soon as my husband was diagnosed with pancreatic cancer, there started to be buzz among the people that I would talk to — patients as well as doctors — about: have you heard about the vaccine? Is there any way to get the vaccine? It feels a little mythological. Can you give us a status report on where we are with pancreatic cancer vaccines?
Dr. Andrew Ko: I'd be happy to. This is certainly an area of interest not just among researchers, but patients themselves are coming to me and really asking about whether they're a candidate for vaccines. The concept of cancer vaccines has actually been around for quite some time, and they come in different forms — peptide vaccines, cellular vaccines, and mRNA vaccines. There are a variety of approaches, but the general idea is: can we give some form of immune stimulant to get the body's own immune system to recognize and fight the cancer?
We think of vaccines traditionally in a prevention mode — for a smallpox vaccine, you're getting a vaccine to try to prevent smallpox. Cancer vaccines are a little bit different because they're not necessarily intended to prevent the development of cancer. For folks who already have a cancer diagnosis — specifically in this case pancreatic cancer — the question is whether vaccines can be helpful in treating it, or more accurately, in preventing recurrence for individuals who have already had their cancer removed. So when patients with more advanced or metastatic disease come to me inquiring about vaccines, that's probably not the right context in which to think about the utility of vaccines. The ones furthest along in clinical development are being incorporated as part of adjuvant treatment, to help improve the likelihood that a person will be cured after completing their definitive treatments.
Alisyn Camerota: So in other words, at the moment, they don't stop the spread of pancreatic cancer once you already have something metastatic.
Dr. Andrew Ko: That's correct. At least at the present time, the ones in clinical testing that have some intriguing data are meant for folks with earlier stage disease who have had surgery — incorporated with their adjuvant chemotherapy, they would receive a vaccine to help reduce the risk of relapse.
Alisyn Camerota: In terms of the research, has the vaccine worked?
Dr. Andrew Ko: The answer is it's too early to tell. There are a few that have been studied in small cohorts of patients, and the results look promising but still preliminary. For example, there is an mRNA vaccine called Autogene Cevumeran, which is created by identifying the so-called neoepitopes in a patient's tumor that has been removed — basically the unique proteins expressed by a person's particular cancer. The results so far show that, at least in terms of proof of principle, patients can mount an immune response to that vaccine. Whether that translates into improved survival or cure rates is the subject of an ongoing large randomized study that our institution and a number of institutions around the country and globally are participating in. The readout for that work is still a few years away.
Another one that's gotten a lot of interest is a KRAS-specific peptide vaccine called ELI-002. That also has very promising evidence showing that patients can mount an immune response after having resected KRAS-mutated pancreatic cancers. The preliminary results with short-term follow-up look quite good in terms of encouraging rates of disease-free survival, but we really need more and longer-term follow-up data to get a sense of whether this is something that can ultimately be approved for widespread use. There's excitement and a lot of scientific validity, but whether that translates into actually making a difference in outcomes for patients, we still have to see.
Alisyn Camerota: And as you know, as soon as a patient gets a diagnosis, it feels urgent. We need something now. A couple of years down the road doesn't really work for pancreatic cancer patients. So that's part of the breathlessness about this.
Dr. Andrew Ko: Totally understood.
Alisyn Camerota: So let's move on from vaccines to immunotherapy. I know that's been a lifesaver in other cancers. What's the status of immunotherapy for pancreatic cancer treatment?
Dr. Andrew Ko: Vaccines are one form of immunotherapy. There are a whole number of different strategies to harness a person's own immune system to fight the cancer. Unlike other cancers that are much more responsive to immune-based approaches — like melanoma, lung cancer, and kidney cancer — pancreatic cancer is known to be what we call an immunologically cold tumor. Efforts to boost the body's immune system to fight the cancer have been met with only very modest success, and we don't yet have any approved immunotherapies for pancreatic cancer.
One area where a phase 3 study has recently been completed involves a so-called anti-CD73 molecule. This inhibits adenosine production within the tumor microenvironment, because the tumor microenvironment in pancreatic cancer is generally very immunosuppressive. If there's a way to release that suppression and make it more receptive to the body's immune system, that might be an effective way to fight the cancer in combination with chemotherapy. The study evaluated the combination of chemotherapy with or without the CD73-targeting drug, and we're awaiting those results — there's a lot of buzz and excitement around seeing them.
A little further down the road, but certainly something with a lot of interest, is cellular therapies — adoptive T cell strategies, CAR T cells, and T cell receptor therapies. These approaches have transformed the way we treat liquid tumors like leukemia and myeloma, but doing the same for solid tumors like pancreatic cancer is still very much in its infancy. The principle is taking a person's own white blood cells — their T cells — genetically engineering them, and reinfusing them to get those T cells to recognize and fight their cancer. Getting those cells to persist, traffic to tumors, and then kill those tumors is what a lot of researchers are trying to fine-tune. Despite limited success so far, there is no shortage of effort and a variety of strategies to get the body's immune system to effectively fight pancreatic cancer.
Alisyn Camerota: Let's talk about something that I think has worked well in various clinical trials — KRAS mutation-targeting treatments. Because so many pancreatic cancers have that KRAS mutation, these seem to be effective. From my limited experience, I'd say not terribly durable, but highly effective when used. Are there other things like the KRAS mutation being targeted in research beyond that?
Dr. Andrew Ko: First, just a word about RAS inhibitors. I think this is going to be the biggest advance in pancreatic cancer we've seen in a long time, because as you pointed out, over 90% of patients with pancreatic cancer have a KRAS mutation. For the longest time, this has been sort of a holy grail — can we target this particular mutated protein? There have been a number of challenges because the KRAS protein has a very smooth surface that's hard to develop inhibitors against, but over the past decade or so, there have been some very innovative strategies to effectively inhibit KRAS signaling.
The early readout of some of these RAS inhibitors looks extremely promising. And while you noted the responses aren't necessarily durable, some of the early patients on those studies have shown disease control lasting one to two years with just an oral drug. That has my colleagues, patients, and myself very excited. I think there's a lot of promise that this class of drugs will ultimately gain approval — we're hoping as soon as sometime this year. I believe they will transform the way we treat pancreatic cancer.
There are other targeted strategies as well beyond KRAS. One with quite promising signals is something called MTAP — a gene that is deleted in about 20 to 25% of patients with pancreatic cancer who undergo genomic profiling. There's a class of drugs, specifically PRMT5 inhibitors, that use a principle called synthetic lethality to take advantage of the genetic vulnerability of these cancer cells due to their loss of the MTAP gene. This shows to be a very promising therapeutic approach for that subset of patients and is advancing in clinical development through a number of different companies.
Another target worth mentioning is Claudin 18.2. There's already a drug recently approved for gastric cancer — an anti-Claudin 18.2 antibody — and a variety of approaches targeting this protein for both gastric and pancreatic cancer, where it's expressed on the surface of maybe 40 to 50% of pancreatic cancers. These include antibody-drug conjugates, bispecific antibodies, and even Claudin 18.2-directed CAR T cells. It's a valid target with a lot of different strategies, and there's a lot of intrigue around promising early results.
Alisyn Camerota: It's funny hearing you speak this language that I used to be fluent in 18 months ago before my husband passed away. It's jogging my memory — the MTAP deletion, the Claudin. I remember hearing about these in the pipeline. Once you're in this world, sadly, how fluent we all become in this language that sounds like gibberish to outsiders — but everyone listening to this podcast will understand what you're speaking about.
Dr. Andrew Ko: I apologize for getting overly technical, but I've found that a lot of patients and their families are very well versed and come in asking questions about many of these specific molecules. It just reminds me that every patient with a pancreatic cancer diagnosis should certainly ask: has my tumor been sequenced? Has it undergone full molecular profiling? We now have so many actionable molecular targets where we can actually do something, and that really should be part of the conversation.
Alisyn Camerota: And for better or worse, when somebody we love gets this diagnosis, we do start speaking this language and have to become fluent in it. So I appreciate you sharing all of that. Let's talk about a screening test, because that's another way to theoretically tackle the deadliness of pancreatic cancer — catch it early enough. As you know, the vast majority of cases are not caught early. How close are we, research-wise, to an early screening test to detect it?
Dr. Andrew Ko: I completely agree that maybe the biggest impact we could have on pancreatic cancer survival rates is to catch it early, or even at its precancerous state, before it has a chance to become fully invasive and spread. The question is first: which patient population should undergo screening? There are certain high-risk patient populations — based on a strong family history or being a known genetic carrier of a particular mutation — for whom screening programs have already been implemented at some major cancer centers. These include regular MRIs or endoscopic ultrasounds to look carefully at the pancreas for very early lesions.
This doesn't apply to the general population — we can't screen everyone at normal risk with potentially invasive or expensive tests. So the question becomes: are there blood-based tests that are more readily accessible? The answer is yes, some are in development. There are multi-cancer panels — GRAIL has their Galleri test, which uses circulating tumor DNA in the blood to try to identify a whole host of cancers, including pancreatic cancer. If you have a positive signal, that leads to further workup with imaging. This has already been tested in tens of thousands of patients with encouraging sensitivity and specificity.
Specific to pancreatic cancer, we don't yet have something ready for widespread use, but there are some encouraging tools in development — primarily blood-based assays. Beyond circulating tumor DNA, there are other approaches, including microRNA that can be detected in the blood, shed by cancer cells either free-floating or packaged in what are called exosomes. A number of research teams have developed panels looking at multiple biomarkers — including CA 19-9, which this audience is likely familiar with — combined with several other novel markers. Together in an array, these show pretty high sensitivity for picking up early stage pancreatic cancer.
Ideally, we want to detect pancreatic cancer at stage I or stage II, where it's still potentially curable — but even better would be catching it at stage 0, at the precursor stage, before it becomes fully invasive. That would be by far the biggest impact. There are a number of brilliant teams working on this, and while it still needs further clinical development, there's a lot of excitement.
Alisyn Camerota: Wouldn't you add to that, Dr. Ko — speaking from my medical expertise, of which I have none — that we should add blood sugar tests to this? I mean, isn't it sometimes the case that a spike in blood sugar, someone becoming pre-diabetic or diabetic when they weren't before, can also be a red flag?
Dr. Andrew Ko: Absolutely. Diabetes is something I think about in two ways. Long-term diabetes itself can be a risk factor and place someone at higher risk for developing pancreatic cancer. But to your point, the sudden onset of diabetes — or even in someone who already has diabetes, blood sugars that were previously well-controlled suddenly spiking and becoming very poorly controlled — I think is worth flagging. It's more the primary care physician managing them who might at least raise the suspicion that there's some underlying cause worth working up further. Some basic clinical factors can raise one's awareness and put up a red flag.
Alisyn Camerota: What is the role of AI as you see it in research and the future of helping with all of this?
Dr. Andrew Ko: Sticking with the realm of prevention and screening, AI offers the ability to comb through very large data warehouses and databases to identify relevant features — extracting that information from clinic notes or laboratory data, which in the past would have required countless hours of manual work. Things like subtle changes in someone's hemoglobin A1c or neutrophil-to-lymphocyte ratio — analyzing these very large data sets might give us clues as to who we should have clinical suspicion of having early pancreatic cancer.
On the other end of the spectrum, the huge amount of data from comprehensive genomic profiling of patients is an enormous wealth of information that AI is really going to help us sift through — especially as we go beyond gene panels to single-cell RNA or DNA sequencing. You're going to have tremendous amounts of raw data to comb through that can be used to look for drug sensitivity, prognosis, and much more. I think we can harness AI for any number of research efforts.
Alisyn Camerota: What have I missed? What else would you like to say about what's happening in the research world or what's in the pipeline?
Dr. Andrew Ko: I've learned not to be too hyperbolic, but I actually think this is an extremely exciting time. I've been working at this for more than two decades, and I think we're at a point where we can see major transformations in how we treat people with pancreatic cancer — transformations that will hopefully make a huge difference in their outcomes.
Some of my colleagues who care for patients with colorectal cancer focus a lot on survivorship. I would love to have that be part of our pancreatic cancer population — dealing with long-term survivors and how we provide the best physical, emotional, and social care for them, because they have the good problem of still being alive many years later. I look forward to getting to that point.
Alisyn Camerota: Me too. Dr. Ko, thank you very much for sharing all of your expertise with our listeners. It's really great to talk to you.
Dr. Andrew Ko: Thank you for having me. It's been a pleasure.
Alisyn Camerota: And thanks to all of you for listening. I'm Alisyn Camerota, your host, and I'll see you next time on PancChat.
Cindy Gavin: Thank you, Dr. Ko and Alisyn, for that informative discussion.
I'm Cindy Gavin, CEO and co-founder of Let's Win Pancreatic Cancer. If you or a loved one has been diagnosed with pancreatic cancer, navigating this journey can be extremely overwhelming, but you don't have to do it alone. We hope you'll explore the many resources available for patients and caregivers at PanCAN and Let's Win.
You can find PanCAN at pancan.org and Let's Win at letswinpc.org.
Together, Let's Win and PanCAN are committed to guiding you through every step of the pancreatic cancer journey, offering support, information, and hope.
Join us next month when we look into ways that pancreatic cancer patients can manage their nutritional needs, including a discussion on using pancreatic enzymes.
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