Transcription:
Updates in Pancreatic Cancer Research and Treatment

Dr. John Leonard, MD (Host): Welcome to Weill Cornell Medicine Cancer Cast: Conversations about New Developments in Medicine, Cancer Care, and Research. I'm your host, Dr. John Leonard, and today we will be discussing some of the latest updates in pancreatic cancer. My guest today is Dr. Allyson Ocean, a gastrointestinal oncologist and pancreatic cancer expert here at Weill Cornell Medicine and New York Presbyterian Hospital. Dr. Ocean’s practice focuses on treating pancreatic, colorectal, stomach, biliary, neuroendocrine, and liver cancers. Boy, that's a big group of areas you’ve got to stay on top of, Allyson.

Dr. Ocean leads numerous clinical trials investigating novel targeted therapies in pancreatic cancer and she's a co-founder of Let's Win, which is an online platform that enables patients, doctors, and researchers to share information on pancreatic cancer treatments and trials that go beyond the standard of care.

So Allyson, thank you very much for being here today and joining us. This is a topic, pancreatic cancer, that is in the news a great deal, people are very interested in, people hear about a lot when it comes up obviously with certain celebrities and otherwise, as well as I know many people have either a personal or family connection to it. So thank you for your work in this area.

So when people first hear about pancreatic cancer, probably more so than many other cancers, not that anybody wants to hear about a cancer diagnosis or it always brings out concern, and worry, and everything else that comes along with it. But pancreatic cancer tends to stand out as something that is quite challenging, and I think people think that that's one that is going to be particularly difficult to treat or to deal with. Why is- I mean, number one, is that true? And I think it is, but why is pancreatic cancer somewhat exceptional or distinct in the way that it's approached and the challenges that it presents to patients, and researchers, and clinicians?

Dr. Ocean: So, you're right, it is the cancer that has the worst prognosis of all solid tumors. It is considered a rare cancer. There are about 50,000 people affected by this disease nationally, unfortunately about 47,000 of them die within a year of diagnosis and it's almost always caught and a lot at a late stage, so it's- by the time someone is symptomatic from it by the time someone's symptomatic from it, it's already almost always metastasized or spread to different organs, and therefore unable to be managed with surgery and considered incurable at that point.

The reasons why it is so challenging to treat stem from the fact that it is diagnosed at a late stage from the beginning, so- and surgery is really the only known cure for this, but we're starting to see better outcomes without surgery, and that points to better therapy in a little bit.

But another reason why the disease is so hard to treat is because the pancreatic tumor, which grows on the pancreas, I think of it like that the tumor is actually like an oatmeal raisin cookie. The cookie is the tumor, the cancer cells are actually the raisins and all the cookie part around the raisins is what we call the stroma or the connective tissue within the tumor. And that serves as a barrier to treatments getting in there to help kill it. So chemotherapies can't penetrate that barrier, radiation can’t penetrate that barrier. The bane of the disease really is that we can't effectively get good therapies in. And that analogy was first described- I have to credit Dave Tuveson of the Lost Garden Foundation in Cold Spring Harbor.

Dr. Leonard: So many- you alluded to the importance of surgery, and finding it early, and at a state where ideally you would find it before it's metastasized and where surgery is practical and effective, but you also mentioned that that's really a minority of patients. So we tend to, in diseases like that, think about screening, as you know well, colonoscopy, mammograms, et cetera. So what's the state of screening? And we'll get into, in a minute, to the hereditary aspects of this because I think that's important, but is there a blood test that people can do? Is there a scan that people can and should do? What are the data around that and why has that, from my take, hasn't really been widespread or not appropriate for most people, but why is that?

Dr. Ocean: So there is no screening test for this disease yet because this falls under a rare disease. That's one of the reasons why there isn't a screening test such as the mammogram to contrast, you know, there's 250,000 new cases of breast cancer in the United States a year versus 40,000 to 50,000 of pancreatic cancer. And so there isn't a screening test yet. There is a blood test that's in development. Researchers all across the United States are working on an early diagnostic blood test that can detect the cancer when it's at its earliest stage so that it could be treated with surgery. So the people who are at risk for this disease are smokers, and a lot of people don't know that, that smoking can lead to pancreatic cancer. Alcohol use can lead to pancreatic cancer. Also people that had pancreatitis, an inflammation of the pancreas over time, can lead to pancreatic cancer.

Probably other than hereditary stuff, which we'll talk about next, the biggest emerging risk factor for pancreatic cancer is actually diabetes. And so now efforts are being made to really bring awareness to doctors, internists, family care doctors that treat adults for regular general health, that new onset diabetes- type II diabetes is a risk factor for pancreatic cancer.

The newest numbers are that approximately 1% of new onset diabetics can develop pancreatic cancer within three years. And it doesn't sound like a lot, 1%, but 1% of diabetics is a lot of people. So that's something that we really are now trying to target that population of people, and educate the doctors that see these patients, and even consider screening blood tests in those patients for- as a population to start a screening in.

Dr. Leonard: What's thought to be behind the connection? Is it that you have a problem in your pancreas that leads to diabetes, and that's a marker? Or is it some other connection there? Any thoughts on that at this point? Or probably not all worked out I guess.

Dr. Ocean: It's certainly not all worked out. Sometimes the pancreatic cancer develops and grows and causes the diabetes because the pancreas isn't working well, and the role of the pancreas is twofold, is to make insulin and also to make digestive enzymes for your food. So if a tumor develops and then insulin production is affected, and then people get diabetes, that's one way. Or the other way is that the diabetes is ongoing for a long time, and then someone has another risk factor leading up to the cancer such as smoking or hereditary incidents, and then so diabetes that has long existed first, and then they get the cancer.

Dr. Leonard: So one thing you alluded to was the issue of hereditary pancreatic cancers, and this comes up in every cancer. You know, “My family member had an individual cancer, what's my risk? What are my children's risk if I had it?” et cetera. What's the connection there in pancreatic cancer? What concerns should people have if they have a family history of some sort, and what testing is done to help kind of sort through risk?

Dr. Ocean: Right. What has happened recently is that we've really found out more information about pancreatic cancer and its links to certain genes that can cause it, and about 10% of pancreatic cancer is considered hereditary. And when it's linked to a gene, it can be linked to a gene that a lot of people don't even think about, but that's the BRCA gene, or the ‘braca’ gene that can cause hereditary breast and ovarian cancer, prostate cancer, but also pancreatic cancer.

Pancreatic cancer can also be associated with something called Lynch Syndrome, which is a hereditary GI cancer syndrome. There are other genes such as PALB2, ATM, STK11; these are all genes that are passed in the bloodline that can lead to the development of pancreatic cancer. And so that brings me back to screening. So if someone is known to carry a gene that predisposes them to develop pancreatic cancer, then those people can be screened, and the children of those people, and the siblings of those people can be screened to see if they carry that same gene. And if they do carry that same gene, then they're at risk for developing cancer, and then those people can enter into screening programs, because screening programs do exist.

Dr. Leonard: So I guess there are two steps. Number one, who should get a genetic test? And then number two, if you have a genetic- one of these genes that you referenced, what do you do about that? And I'm sure that's all kind of influx, but what do you tell a patient? Or what guidance do you have for let's say people listening that have a parent or a sibling, let's say with pancreatic cancer? Should they get genetic testing within that in broad way? And then what do you do with that information from the standpoint of screening? And just in a nutshell, because I'm sure it's very nuanced and a longer discussion.

Dr. Ocean: Sure. The NCCN, which is our organization that provides guidelines for treatment and for screening has recently announced that every patient diagnosed with pancreatic cancer should undergo genetic testing. And the reason why is because we are picking up more and more genes that can cause the disease. And if we can pick up the genes earlier, then we can screen people for those genes.

So now everybody who gets a diagnosis of pancreatic cancer should get genetic testing. Then if a patient is found to have a gene, then their siblings and their children should get tested because they have a 50% chance of passing on those genes to their children. If anyone has a family member with pancreatic cancer, a first degree relative, either a parent, or a grandparent, or a brother, or sister with pancreatic cancer, those people should be alerted that they probably should have testing done.

There is an entity called hereditary pancreatic cancer where it runs in families, but they actually don't even have genes that we can detect through blood tests. But they should know that if pancreatic cancer exists in the family, they should ask their doctor about what screening they could get done or at least get a referral to a genetic counselor. I think that that should be the first step.

Dr. Leonard: Okay, and then the screening for pancreatic cancer in the person themself who has this risk, I'm sure that's kind of a moving target, but is it imaging test primarily?

Dr. Ocean: Since there is no official a screening test for this disease, all of the tests that you would do such as an MRI or an endoscopic ultrasound or something like that to diagnose it, none of that's covered by insurance. But if someone enrolls in a trial that is a screening study, then all that's covered.

The way those studies work is that people who have these genes who are known to be at risk get an MRI, which is not a test that gives them radiation, but it follows them. So an MRI alternating with something called an endoscopic ultrasound, which is a scope down into the stomach which reaches the pancreas to look to see if there are any small tumors that could be there.

Dr. Leonard: So I think that's one of many examples, and I think you will get some more in a minute or two, of where clinical studies and clinical trials and participating in research to help answer these unanswered questions really as to what the best screening strategy is. And also to not only advance the field, but perhaps help an individual patient who will have, through one of these screening studies, an opportunity to get screened and perhaps pick something up. So it sounds like a great opportunity for people to look into if they fall into one of these categories.

Dr. Ocean: Definitely.

Dr. Leonard: So I want to get into some of the new therapies, but very briefly, the Whipple procedure I guess is the main surgical treatment. Just a word or two about that. I know you, like I, are medical oncologists who don't do those procedures, but you've had lots of those patients have those. And I know that's a big operation. Just in brief, what does that generally entail before we get into kind of the systemic and radiation treatments, et cetera?

Dr. Ocean: Sure. The operation is aimed at removing the cancer fully, and because the pancreas is embedded around the small intestine, and close to the stomach, and close to the bile ducts, and close to the liver, all of those organs are involved within the surgery.

So basically the surgeon has to remove the cancer and reroute the plumbing in that area so that the as part of the pancreas is removed, the bile ducts have to be rearranged, the stomach has to be reconnected to the small intestine, but it's a surgery that is potentially curative for pancreatic cancer, and most people who undergo the surgery survive the surgery and can live a normal life after having a Whipple. There are some misconceptions that people have to be on feeding tubes or people can't eat the same way ever again. Not true. Once someone heals fully from the operation, they can live a normal life.

Dr. Leonard: So you alluded earlier to the challenges of getting drugs, chemotherapy or other drugs, to make them effective in treating advanced stage pancreatic cancer, which as you mentioned, a large percentage of patients have. So what are some of the exciting new areas that are moving the field forward, or potentially moving the field forward, that you think whether they've been presented at recent meetings such as ASCO, or things you're working on here, where are some of the key areas of most promise from your perspective?

Dr. Ocean: I think the excitement in the field really comes down to genetics again, because we want to identify the genes that are driving these cancers, and then figure out the drugs that best inhibit these genes or target these genes. And actually here at Cornell, we're doing really important work at the Englander Precision Medicine Institute in creating what we call organoids for pancreatic cancer. Organoids are three dimensional tumors that are grown outside of the patient. So a biopsy is done of the tumor, it's put into a medium that mimics as if it's still in the body, and this tumor grows outside in the lab, and once the tumor grows to a full size, that tumor can actually be sequenced, which means that we can actually get the genetic code of the tumor. And then once we get the genetic code of the tumor, then we see what genes are driving it, what genes are turned on or turned off that could be targeted with certain drugs.

But another important aspect of having an organoid for someone's cancer is that you can do drug testing on it. So thousands of different drugs can be tested on this cancer outside of the body to see does this work? Does this not work? Instead of kind of trial and error on the person. Because many times we give chemotherapies that are considered standard chemotherapies, but they don't work because someone's cancer is unique and may not respond to drug A, but would respond to drug B. But we don't know that until we try. But now we can try testing drugs outside on this organoid, and kind of experiment on that, and then have it guide therapy in the patient.

Dr. Leonard: I think that's great, what you've alluded to, and we've had other episodes of this podcast talk a little bit more about precision medicine in more detail. I think we're all- obviously we have some great examples of where that's made a difference, obviously a long way to go in a number of different areas as well.

Are there one or two kind of categories of drugs, let's say, that you think are particularly interesting that if a patient is out there you might want to learn more about? Any thoughts on that?

Dr. Ocean: So chemotherapy is an important tool in this disease. We're always trying to improve upon the outcomes that we get with chemotherapy alone. I think some of the exciting drugs in trials now are drugs called stem cell inhibitors. There are also- specifically to certain types of pancreatic cancer such as the one that is attached to the BRCA gene. We use drugs called PARP inhibitors, and that's an exciting new treatment that has been shown to be effective in the BRCA mutated cancers.

We actually have a clinical trial here that's looking into the role of high dose IV vitamin C as therapeutic in pancreatic cancer because the main mutation in pancreatic cancer that exists in 99% of them is a mutation called KRAS, and right now there are no drugs that directly target KRAS. However, high dose vitamin C, through the work of Dr. Cantley here, has shown that high dose vitamin C does get into the cell that carries this KRAS mutation, and this also applies to colon cancers as well, that had the KRAS mutation.

So anyway, vitamin C gets into the cell and basically serves to starve the cancer cell of its energy source, and that's how it dies. So instead of chemotherapy working on the genes and killing the DNA so that the cell dies, approaches now that are going on in pancreatic cancer are looking more into the metabolism of the cell as to how does the cell get its energy source, and vitamin C is one of those ways.

We’re also about to open up a new trial here of a drug called SM-88, which also works on the metabolism of the cell, and so that's about to open too. A lot of patients ask me about immunotherapy. Unfortunately, immunotherapy is not ready for pancreatic cancer. The problem is, is that the immune system doesn't really care that you have pancreatic cancer, so it doesn't focus on it. We're working on strategies to make the immune system more aware of pancreatic cancer, but I get that question every day, unfortunately. I wish that it was such a game changer as it is for many other cancers.

Dr. Leonard: Great. Well, just before we finish, I just wanted to ask you briefly about your involvement in the Let's Win project and program, which I know you've been really working hard on. Tell us briefly about Let's Win and how it works with the pancreatic cancer community to kind of move things forward.

Dr. Ocean: Sure. About four years ago, a patient of mine had pancreatic cancer and she was given this devastating diagnosis, and the message that she was given was, “We can't help you. You're going to die very soon from this. Get your affairs in order. I wouldn't even bother with treatment.” And she didn't accept that what was told to her, and she came to me and said that we need to change the conversation about this disease. And her name was Ann Glauber, and she had three years of living with pancreatic cancer. She unfortunately did pass away, but all of her treatments were based on science and clinical trials. And we came up with a platform called Let’s Win, which the goal of it is to bring the latest science that is being done in pancreatic cancer into patients' hands faster. And the way we do that is we have three prongs to it.

Patients submit their stories of treatments, clinical trials, even treat standard therapies or stuff that goes beyond standard of care. People that are doing well and living well with advanced pancreatic cancer, they submit their stories so other people can read about them and see that they are doing well with this disease.

The second part of Let’s Win is that we interview scientists about their research and put it out there in a very readable, easily digestible way so that patients and doctors that aren't even experts in it can know what the latest research is.

The third way is also highlighting clinical trials, and we're highlighting trials that are ongoing in the disease.

So it's patient stories, it's interviewing the scientists and doctors, and clinical trials. And all of this is on the website, and it's all hyperlinks so people can click on a story and get information that's going on, let's say in Texas, or in California, or in Canada, it can be anywhere.

So- and all of this is all linked together with all the institutions that are leading the trials and leading the research. And so patients get this information very fast when they need it the most, and that's the crux of Let's Win. Anyone who's diagnosed with pancreatic cancer, it's our goal that they know about this organization. We've just recently become a nonprofit, and we hope that doctors will start to refer patients to the site. It's www.LetsWinPC.org.

Dr. Leonard: Great. Well I think that's, to some degree, how you summed up was a little bit of I guess a parallel to how we've talked about the disease in that it’s obviously a very challenging and difficult thing for patients to deal with, but there's a lot happening. You have to engage yourself in the science and in the latest technology, and obviously a referral center that’s seeing these patients and participating in a new clinical trials and new scientific studies that are trying to move the field forward. So thank you for all your work in this area. It's really a bit of great discussion, and thanks for joining us today, and I hope patients who are interested in pancreatic cancer, look into Let’s Win, and get more information there.

So with that, I want to draw our session to a close and again, thank you for joining us today. I want to remind our audience that you can download, subscribe, rate and review Cancer Cast on Apple Podcasts, Google Play Music or online at www.WeillCornell.org.

We also encourage you to write to us at CancerCast@med.cornell.edu with questions, comments, and other topics that you'd like to see us cover in more depth in the future. That's it for Cancer Cast: Conversations about New Developments in Medicine, Cancer Care, and Research. I'm Dr. John Leonard. Thanks for tuning in.