Sandy Liarakos:
Hello everyone and thank you for joining us today. A warm welcome to the Salk Institute’s Power of Science virtual program, on Conquering Pancreatic Cancer. My name is Sandy Liarakos, and I’m Senior Director of External Relations in the Salk Cancer Center, at the Salk Institute, and I’m very pleased to serve as the moderator for today’s program. We thank you for your interest and your support for our Conquering Cancer Initiative.

Before we begin our program, we would like to share the COVID research that is taking place at Salk. Of course, this is front of mind for all of us, and we wanted to share this. For more information, you can visit this web page. As a follow up to today’s program, we will also be sending this link to you, along with resources that Dr. Evans will be sharing about his presentation. We are also recording today’s program and will be sending that to you, to share with your family and your friends.

As part of today’s presentation, Zoom has a new feature, providing closed captioning, and we’ve included the "how to" slide, noted with the yellow arrow. To enable this feature at the bottom of the screen, you can click, and that will give you a transcript of today’s discussion. Today’s program is interactive, with time for a Q&A at the end. We’ve already received many questions from some of you this past week, and we look forward to answering those. You can still send your questions, and please enter them at the bottom of the screen, in the Q&A, and we look forward to answering those.

So that we can continue to follow a safe distancing, Dr. Evans is in the Trustees’ Room at the Salk Institute, and I’m coming to you from my home. To lead off today’s event, we first wanted to share a message from Dr. Rusty Gage, President of the Salk Institute.

Rusty Gage:
Hello everybody, and welcome to the Power of Science Lecture Series. I’m Rusty Gage, Professor and President of the Salk Institute. I want to personally thank you for your interest in Salk research. In this interactive webinar, we’ll share exciting advances and cutting edge discoveries. We’re reminded during these sobering times of how critical basic science research is to our health, our community and the globe. It was the basic scientific research of the institute’s founder, Jonas Salk, that lead to the first safe and effective polio vaccine, saving countless lives. At Salk, well renowned experts in immunology, aging, cancer, plant biology and other topics, are similarly working to tackle some of the most pressing problems of our time.

In this lecture, you will learn more about Professor and Director, Ron Evans’ important work on pancreatic cancer. Pancreatic cancer is a devastating disease, with only eight percent of patients surviving more than five years. As a part of the Conquering Cancer Initiative, Professor Evans has made significant break throughs in using a vitamin D derivative, in combination with immunotherapy, to help combat pancreatic cancer. He will be sharing clinical trial updates on his research. Thank you all for your continued support and interest in the Salk Institute. We look forward to the day when we can see on campus again. Have a good evening.

Sandy Liarakos:
Thank you Rusty, and I’m so pleased to introduce our speaker today, Dr. Ron Evans. Dr. Evans received his undergraduate and PhD at UCLA, and was a post-doctoral fellow at Rockefeller University. Dr. Evans is Director of the Gene Expression Lab at the Salk Institute, and holds the March of Dimes Endowed Chair. He is a member of the National Academy of Sciences, and the National Academy of Medicine and is referred to by Google, as one of the 50 most, influential scientists in the world today. During his 41 years at Salk, he has received numerous awards. Most recently, this year, the NOMIS Distinguished Scientist and Scholar Award. Dr. Evans and his team are known for their work on genomic networks of health and disease, leading to new therapeutic approaches in both diabetes and cancer.

The focus of our program today is pancreatic cancer. He is determined and relentless in these research pursuits. It’s a real pleasure to introduce you to Dr. Evans, a world renowned scientific leader. Ron?

Ron Evans:
Along with Rusty, I’m happy and welcome everyone who’s out there listening. I really appreciate the time that you’re putting to this, and also Sandy for her kind introduction. What I’m going to do today is tell you about some of the work that’s going on in my lab, on pancreatic cancer. This is one of the most feared and deadliest cancers that we know of. After decades of work on it, it’s still considered untouchable. It’s highly lethal and poorly understood. Because it’s one of the deadliest diseases, diagnosis of pancreatic cancer is a crushing diagnosis. Because it’s considered untouchable, it is really a sledgehammer when that happens.

Let’s think about how we approach this cancer. If you look here, it is the third leading cause of cancer deaths, and most patients come in with stage four diagnosis, that is it’s metastatic. Then there are other forms that are localized in the pancreas and other components that are more complicated about its appearance. Here’s why it’s one of the most deadliest. Most people come in with metastatic and the average for that population is 4.5 months. In one year, more than 80% of people diagnosed, have passed away. This is a very aggressive cancer. Not only is it feared, but it is just tremendously hard to deal with. One of the reasons it’s hard to deal with, is you can’t find it early. The nature of early diagnosis for any cancer is key to getting to it and changing the game.

You don’t go into your doctor and say my pancreas hurts. The symptoms are often vague, and similar to other kinds of diseases and so it is this kind of change that doesn’t really tell you what’s going on, until you get the actual diagnosis. One of the interesting features is that in adults, about 85% gets some form of rapid onset diabetes. Remember, in the pancreas, part of it is for digesting food, part of it is for controlling sugar through insulin and the islets. My lab studies islets. We study nutrient control and energy control. We study pancreatitis, which is inflammation of the pancreas. It occurs in many people and it can be lethal, and it can lead to pancreatic cancer, and we study pancreatic cancer. There are three diseases of the pancreas that are all tough and important to study.

For pancreatic cancer itself, surgical removal is just not available to most people, because of the spread of the disease, less than 20%. Eighty percent can’t do it. Interestingly, if you look at the transfer, most of the major cancer is prostate, colorectal, and breast, you see that they’re going down, as is true for lung. Pancreas is going up. We do not know why it’s going against the trend, but it’s significantly getting worse. Of course, we all know about Ruth Bader Ginsburg. She was diagnosed, actually, early in a medical exam. She was able to live a long time, perhaps not quite long enough. It’s a terrible loss. Also, Alex Trebek. He put up an incredible battle, very positive and very determined and made it for about a year and a half, which is actually pretty substantial. It’s not obviously anywhere near good enough. Even with surgery, prognosis is rarely changed.

For this cancer, we have to really rethink. As I show here, important challenges include: improve early detection. We don’t have a good way to go. Understanding why therapies fail. You can learn a lot from failure and that is one of the key things to keep in mind. Identifying therapies that are designed for pancreatic cancer, mostly and only gets therapies that are designed for other cancers, like breast cancer or lung cancer, and then go let’s see if it works on pancreatic cancer. It doesn’t. Think differently. You can’t be linear. You can’t just say let’s just take a cocktail and see if it works. You have to really have a plan that is a way to go forward, and to apply what we think is the most powerful force on earth, which is knowledge. Knowledge comes from the science that we do. That’s the most powerful entity. By thinking differently, I mean change the game. I call this inside out versus outside in. If we think about how to deconstruct a complicated problem like this, it takes a way of sort of envisioning what your goal is.

If you look at the nature of the tumor, and it’s environment here. The tumor is encased in a living shell of fibrotic cells, that are producing inflammatory components, and they’re being tied up with the fibrosis. It creates a lot of pressure as that tumor is growing, which excludes blood flow, excludes drugs coming in and creates this incredible shield or a vault. It is protecting this. This is what we call the Stromal Barrier. It’s a major physical problem, but also it is supplying the energy. It’s the fuel supply line for the tumor to grow. Our idea was if it’s a fuel supply line, just like in a military battle, if you cut the supply line, you’re going to wipe out the battle. We’re thinking how do we reprogram this? We discovered using molecular genetic techniques in my lab, that the on/off molecular switch for this Stromal Barrier is something called the vitamin D receptor. It is the target that controls the function of vitamin D in the body.

As we look at this, because of the way this tumor is designed, the blood vessels get compressed and the T cells come and they try to find the tumor, but instead they find the barrier. The barrier is normal cells in the body, it’s not mutated cells. They’re not tumors, so they can’t see the tumor. They’re around looking, but they can’t get there. We said, can we unlock this barrier and overcome some of these components that have blocked therapy. We’re going to try and unlock it by taking advantage of this master regulator, vitamin D receptor, and restoring vitamin D to the system. In this environment, there is no vitamin D. There’s an enzyme that breaks down natural vitamin D, so it’s completely vitamin D deficient, but that switch is still ready to be turned on. When we add a chemical form, it is not broken down by the tumor, we can turn the vitamin D receptor back on.

The idea is illustrated here. If the tumor is encased in this protective area, can we use the vitamin D receptor to decode the protection mechanism, and expose the tumor, so that drugs and cells can come in and attack it, and change the game? We start this therapy that I’m illustrating here, basically from the outside in. We’re not trying to attack the tumor cell first. We’re actually modifying the Stromal Barrier. When we do that with vitamin D, you see the barrier is broken up. When that is broken up, what happens is that now cells become available to the outside. Now, the T cells can infiltrate and there they go in. We see more T cells in patient material, that has been treated with vitamin D therapy, based therapy.

Those T cells are not necessarily active. The way that you activate T cells is with something called checkpoint inhibitors. This is a part of immuno-oncology. These checkpoint inhibitors are anti-bodies that come in and they turn the T cells on. They lead to the destruction of the tumor. This is a process that we are trying to overcome, because in the patient population, checkpoint inhibitors have not worked at all in human pancreatic cancer patients. Why have they not worked? Well, because you have not unlocked the entire space, or the shield. They just bounce off basically. If you want immuno-oncology to work, these powerful checkpoint inhibitors, you have to have a strategy to attack the barrier first. With that, we made a proposal to Merck, in combination with Stand Up To Cancer, to support a trial designed here at Salk, in which we would give patients Merck’s KEYTRUDA, pembrolizumab. This is one of the major checkpoint inhibitors. It’s used in oncology, in combination with our paricalcitol, vitamin D, therapeutic drug.

In a simplified way, I’m just showing you results from that trial. It is an ongoing trial. These are individual patients that are in our trial. If there’s an "X" that means that they’ve passed away. If there’s an arrow, those patients are still going. This is a double blinded study, so we do not know which patients have received the therapy or not, neither does Merck. We will not know that until the trial is completed, yet you can see here some patients are almost two years out. Of course, we’re hoping that that’s part of our therapy, but whether it is or not, this gives us a lot of information, because each one of these patients, we’re going to be getting tumor material. It is extracted from them. Each patient has a story to tell, and the story from that patient is usually lost. Most patients, you don’t get to really study them in any detail. This is a failure of the system. There’s a lot of information, both in failure and in success, and we want to understand how we can use that.

We call this digitizing cancer. This is a way of deconstructing the problem, from a very sort of gritted and directed process, that we have designed in the lab, that allows us to sort of deconstruct this in a specific way. What I’m showing you here, are two needle biopsies, they’re really very thin. These are very magnified, from two of our patients, in this trial. We’re using a special technology that’s relatively new. It’s only in about a dozen places around the country. We have one here at Salk. It allows us to actually turn these biopsies into colors. We look at nuclei, because they’re blue. We can look at the tumor because it’s green. We can look at immune cells because they’re red. We can look at the fibrotic fiberglass, which are gray. You can see them here, for example. You can see green here. We can break this down. We can also look at hundreds of other components in these biopsies, in three dimensional spacial resolution, how these cells relate to each other. Also, thousands of RNA transcripts. These are products from activated genes, that we can look at as well.

From these biopsies, we can extract a huge amount of information that wasn’t previously possible. This is really very valuable. In context, pancreatic cancer, we may be the only ones doing it, because the other machines are probably doing other types of things. We, along with this, developed a novel technology that we call SCAN. Scan is Selected Capture and Analysis of Nuclei. The importance of that and this digitizing cancer concept is it allows us to take the biopsy material, and take the nuclei from all the cells that are in there, and we sort them in a special type of machine, that separates out because we can identify the cancer cells. Here we’re going to say that they’re in green. As they come through the sorter, the green cancer cells get separated from the red stromal cells. The stromal go here, and cancer goes here. Now, we can cleanly look at what’s happening in the two components, when you give the drug and the therapy.

This is key. We’ve never been able to have this resolution or this ability to actually dig into the details. This is one patient. We’re going to be doing it with all the patients in our trial. However, Merck doesn’t really want that information. That’s interesting. They just want to know if their drug works. It is a little bit surprising, but from that information, we will get a road map that will change the way in which we think about this cancer, how it progresses and how it might be treated. One of the things that Merck is not interested in so much, this is how you advance the field. They’re a drug company. They want to develop the drugs. They’re not there to deconstruct and digitize the cancer.

We’re looking at the genome and all the details of how this cancer gets powered up. Cancer, as it grows, needs energy. Part of this process of the digitalization of this, digitizing this, is to look at the genes in the fuel supply line, that is these fiberglass, that are making the shield. They are powering up the tumor as it grows. Normally, a normal pancreas has its source of energy coming to it, and we show it as a power grid that comes from a source. We call these super enhancers, because we got a special trial again from Stand Up to Cancer, on looking at the top one percent of genes in tumor cells, or in normal cells, that control the power circuit. We still are running that trial.

Through that trial, we can create sort of the nature of that network or that grid. Here it is going to the normal pancreas. What we did is we found that by deconstructing it, there’s certain genes in that top one percent, that are these genes. You don’t have to know their names, but these are three of them. We like these three genes through a particular reason. The reason is because this one stabilizes this particular gene, which is an enzyme, and then this gene acts on the one below here. One stabilizes that, and this comes here, target that and that leads to the normal energy flow into the normal pancreas. In the context of cancer, now, instead of having a house, you have like a skyscraper. That’s what you have, the energy demands of. This grid is not enough. You get an oncogene, we find, turns the grid on, ramps it up. This oncogene is called MYC, very common in pancreatic cancer. Now, the entire tumor is being lit up and this is part of the fuel supply line, the energy that is driving this process.

So, we then ask, using genetic engineering techniques, can we determine whether these genes are important. This is a scan of the gene, in its natural place in the genome. We went up about 10,000 nucleotides, and found a little green region. This is a super enhancer. We decide to delete it, take it out, using CRISPR technology, which is the genetic engineering tool. It shows it here as scissors. That takes this off the grid. Now, the source of energy for this, is being decreased. What happens is that the tumor, normally growing here in yellow, is now down here when we make that snip, all right? It’s not sufficient to knock it out because MYC’s still getting power and it’s able to power this part down here.

Now, let’s cut out the next part. What happens when we make that cut? You see what happens again. The tumor really is struggling because it’s not getting the power. We keep going through this entire process, with each of the genes. Now you can see here, again, the cut and what happens. We are now describing a key energy network, that can be genetically engineered to be proven what it’s doing. One of the questions is can it be drugged? What I want to say is that’s what we’re doing, basically, is because one of these genes happens the PRMT1, is the target of a drug that’s actually in clinical trials. We actually got the drug and tested it in our system. What you see here is this drug simply brings the tumor down to a more than 50% reduction size, just with this one drug. Now we’re not snipping the genes we’re actually giving an orally active drug. It changes the tumor from looking like this here, to looking like this here.

We’re excited by this approach, giving us entirely new insight into this disease this is digitizing the cancer, giving us huge amounts of information, where before we had very little. Now we’re having an abundance. We have to use machine learning and giant computers to collect all the data that we’re getting, but it’s really interesting. Just to say what’s coming out of a place like Salk. It’s basic research, but the impact that we’re having in the clinical world is real. We are a small institution, but because we’re so focused on what we do, we have a big impact.

This is an example of just the clinical trials and the centers that my lab has been working with. You can see that they also go all the way around the world. This has been a great area for us to be in. I want to just end by mentioning that hope is real, that the ability to understand this cancer may be now upon us. So, if we can look at this curve here, this survival curve. You saw this before, 4.5 months for stage four cancer. I want to show you this, is Dr. Stephen Bigelsen. He’s a physician, Rutgers Medical School. He was diagnosed with pancreatic cancer. It’s not his area. Knowing that, he knew was a death sentence. He, as a physician, he went to the literature, found our paper, found the trial that we were doing and prescribed the drugs to himself. His oncologist gave him our therapy and what you can see here is since he took the therapy, and from when he started the therapy, he almost immediately started improving. It took six months for all of the signs of his disease to go down. He’s now four years out, and cancer free, that is, no evidence of disease. He’s still taking the modified form of the vitamin D as a supplement basically, and still doing really well.

Lots of things are possible. He’s one of an example. I get contacted every week by patients who are looking at this in many of their own trials, working with their own physicians. This pancreatic cancer work began in our lab a number of years ago. We were able to get Stand Up to Cancer’s support and Geoff Wahl and Tony Hunter joined the crew. Dannie Engle, recently, is our fourth person. Michael Downes is a key person in my lab for helping to run this project. Sue Kaech is an immunologist, joined us. That’s the fifth lab. The sixth lab is Reuben Shaw and the seventh is Ed Stites. So, it’s not just a lab. We have a program that we’re developing in this space. We hope that together, we can make a difference.

I want to thank our partners, because you can’t get this funded by NIH. They won’t fund these speculated programs, but that’s what we need in a place like Salk. We’re dependent on donors. If you want cutting edge research, you’re way ahead of what the funders will give you. I want to thank the Copley Foundation, the Freeberg Foundation, the Lustgarten Foundation and Stand Up to Cancer, Wasily and Pedal the Cause. These are all sources that have really supported our program. It makes a huge difference. We are really on the road. We have momentum. We know what to do and how to do it and we have the ability to do it. At that stage, I’m going to stop. Thank you all for listening, joining this call. I will be delighted to answer any questions that you might have.

Sandy Liarakos:
Thank you Ron, that was great. We have a lot of questions actually, so I’m glad we have the time to do this. The first question actually is: What’s the best way to support this research through donations? We do have a link on our website for the pancreatic cancer program. We do have lots of philanthropic needs, especially as we grow this program and expand. I don’t know, Ron, if you want to take a few minutes to talk about… I know we just thanked the foundations who support your work, but this is definitely a critical time where we need the philanthropic support.

Ron Evans:
Well, I think that’s a first. Thank you everybody for joining, listening to the presentation. It’s my pleasure to do this and to give you a glimpse into some of the work that my lab is doing, in this really challenging cancer. Sometimes, the more challenging it is, the more focused you get. We are truly focused on this. We believe it’s going to have a very big impact, the work that we’re doing here. I am really delighted that you’re here listening to us. On the other hand, most of the work that we have done is not from any kind of government support at all, it’s through private philanthropy. I can’t tell you how big that impact is. You want to have cutting edge research. This is really about accelerating the process of getting discoveries. The government doesn’t do that. They’re really relatively conservative.

This is all about moving forward at a quick pace. That requires private support. I think all of you probably know that the more support you get, the faster you can go. We want to get there as fast as possible. It really is a financially driven process. We have the ideas and the way in which we think we can get there, is sort of thought of as a moon shot, sometimes. That’s what Joe Biden actually has been heading, to get there. For any kind of cancer, you still have to sort of break through the sound barrier, and then be able to get to the stratosphere and then be able to push yourself ever farther. You need the power to accelerate through that. That’s what we need, I think, for our philanthropy. The more that we can break that barrier, the faster we can get there. We are on the heels of this cancer. We are really close. I think it’s going to be afraid of us. Whatever we get from that, is going to really impact other cancers, so we really encourage, if you can, to support this program. It is really one that we think is going to make a difference.

Sandy Liarakos:
Right. Thank you Ron. I will plan to send that link along with all the other resources that we talked about. Let’s start with one of the questions: Has research been done in a CHEK2 gene mutation, in regards to pancreatic cancer and the family inheritance, so a genetic predisposition?

Ron Evans:
Well, CHEK2 is a gene that checks cell proliferation, cell division, cell growth. When that’s mutated, cells have an increased tendency to grow. It’s commonly mutated in a number of cancers. A study was done at the Mayo Clinic and out of 96 patients, two patients were found to have a CHEK2 mutation. So, it is there, but it’s not super common. It’s a good question because most cancers collect a number of mutations, to be able to become strong and very lethal ones.

Sandy Liarakos:
As a follow up to that: Do you recommend genetic testing for someone with pancreatic cancer, to inform other family members?

Ron Evans:
Well, simple answer is yes. The second statement is absolutely yes. It’s been shown, through a study, that if you get the patient coming in with pancreatic cancer, it was done to then look at as many family members as possible. Significant numbers of family members were found early, to get early diagnoses from that. This is definitely encouraged. If someone in your family has it, it’s good to communicate with the family and encourage them to get tested.

Sandy Liarakos:
Okay. Are there any precursors or signals, or markers, to evaluate before active disease?

Ron Evans:
That’s one of the most important areas to address. There is at least one, which is called CA19-9. This is a type of circulating factor. It’s actually produced by the tumor. It is a detectable molecule, and hospitals can measure it. Typically, it’s only measured as an indicator of therapy during a pancreatic cancer treatment. By the time it’s been used, it’s looking at the disease in place. Yes, you could test in advance, but to do that would require insurance companies to want to test 300,000,000 people. They don’t want to pay for that. You could get it done if you want, on your own, and you probably would have to do it annually. That’s something to consider. It’s a very good question. We need other biomarkers that are a little bit easier to test. We think that that’s going to be a key in serious effort, as part of the program, including work by Danni Engle, who’s very interested in early detection.

Sandy Liarakos:
Okay. What is the connection between pancreatic cancer and colon cancer?

Ron Evans:
Well, first keep in mind, the pancreas and the colon are coordinated in what they do. They are physically linked, and they come out of the same developmental lineage. They’re all about processing of nutrients and controlling energy. It may not be surprising, they share a number of commonalities, in terms of cancer. They also have some things that are relatively unique to each tissue, because they’re not doing the same thing. For example, the oncogene that I mentioned in the presentation, is common to both colon and pancreatic. Both are also relatively resistant to immunotherapy and so it’s a very diff- Colon cancer and pancreatic cancers are two of the top three most lethal. They’re very difficult to treat and typically diagnosis is a true sledgehammer to a patient.

We have also been working on colon cancer. We had a major paper last year, and another one that is coming out of a new approach to think about therapy in that disease, something like the vitamin D receptor concept that we mentioned, but it’s another closely related receptor, with another type of ligan to activate that. We’re excited about potential therapies for both these cancers.

Sandy Liarakos:
In regarding the vitamin D treatment, there’s been lots of questions from our attendees. We know that Dr. Bigelsen, who you shared, took very large doses, I think maybe through an IV. For us, as kind of a preventative, how many milligrams would you recommend that we take, since we know that a lot of us are deficient in vitamin D anyway? What’s your advice on that?

Ron Evans:
Well, whoever asked the question is correct. A lot of people are vitamin D deficient, for a lot of reasons. It is an essential vitamin to be taking. It’s considered to be sufficiently essential, along with vitamin A, to be allowed to be fortified into food and cereals and milk and other things. The reality is, we don’t get enough of it. The typical average recommendation has been literally 100-400 international units, which is I believe low. The Endocrine Society recommends 1,500 IU’s, or international units, daily. I personally take 4,000. This is not a harmful molecule. Keep in mind, you need to get some sun exposure. If you couple vitamin D with a little bit of exercise, and get a little bit of sun, in 15 minutes, that’s a huge impact and benefit to your body. The other thing to keep in mind is pancreatic cancer patients are very, very, very deficient when they come in, vitamin D deficient. The few that are taking supplements, actually have a known better outcome.

The same is true for COVID. If you were taking supplements with vitamin D before you got the disease, you never go to the ICU. The ones that go to the ICU are very, very low in vitamin D, the maximum vitamin D deficiency, and they don’t take supplements. Keep in mind, you can control some of this with daily dosing.

Sandy Liarakos:
I just wanted to clarify, thank you for clarifying the very high amounts. This is something that we can just get over the counter, we don’t need a prescription.

Ron Evans:
You can get over the counter everywhere.

Sandy Liarakos:
Okay.

Ron Evans:
It’s relatively cheap.

Sandy Liarakos:
Okay, great.

Ron Evans:
Yeah.

Sandy Liarakos:
Okay, super. Another question: Is there a pre-existing condition like diabetes, which is more prevalent in leading pancreatic cancer?

Ron Evans:
So, say that again?

Sandy Liarakos:
I know, in your former slide, you had talked about a rapid onset of diabetes. This question is, and perhaps you already answered it: Is there a pre-existing condition like diabetes, which is prevalent for pancreatic cancer. Maybe is there another-

Ron Evans:
Yes. That’s relatively… There’s two parts to that answer. One is, one of the leading indications is something called pancreatitis. This is inflammation of the pancreas. This is a tough disease. It’s also one that we have worked and published on, and also another one that Danni Engle’s lab and ours are interested in, as well as Geoff Wall, actually. In this disease, inflammation of the pancreas causes great pain and sort of a poor functioning of the pancreas. Over and over again, it also wears down the pancreas and creates scarring and is a major risk factor for progressing to pancreatic cancer. Pancreatitis is very hard to control and mostly it’s treated with care and over the counter types of therapies. It doesn’t have a very good treatment. It also can be lethal. That is a major risk factor.

The other component is not a big early component. Adult on-set, rapid diabetes is a hallmark in many patients who come in with pancreatic cancer, however, they already have it. The coordination of the diabetes and the pancreatic cancer means that it’s relatively already active. It’s still, you can get it earlier, if you do get that indication. It’s important to keep in mind that rapid adult on-set diabetes should be checked for pancreatic cancer. Sometimes it gets missed and just treated as diabetes.

Sandy Liarakos:
Mm-hmm (affirmative). I know you had covered some… This question is: Are there lifestyle factors and changes that improved one’s chances of not getting pancreatic cancer? I know you talked about the vitamin D. You talked about sun exposure. You talked about exercise. Are there other things that you would give us as recommendations that we can actively make part of our daily lifestyle in order to prevent this?

Ron Evans:
Well, I have to say lifestyle is important and a few things that are challenging in our society, is technology, computers. We wind up sitting at our desks, even Zoom. We wind up, with technology, sitting more. Simply getting up and moving is really important, sort of circulating your blood. I can’t tell you how important that is. Even a regular walk or a little bit of a brisk walk, that’s a very helpful thing to do. That’s not really exercise, but it’s getting blood circulating. That really changes the game for risk. A little bit of exercise. High fat diets are obviously a major risk factor.

We’ve been studying, just published a paper on why high fat diets are risk factors. In fact, the concept of risk is a word. The word risk is actually hides what is really going on. You can calculate risk, but it doesn’t tell you why one thing or another is risk. It doesn’t tell you why high fat diets are risk, or why exercise improves. It may seem logical, but we have actually studied this, and had a major paper recently, about deconstructing risk, from a scientific point of view. When you understand that, you then can begin to lower risk, from scientific strategies, as opposed to ways in which we don’t fully understand. It’s a great question, and I am really interested in understanding risk itself, from a molecular genetic point of view. It is a real thing, but the number doesn’t really help our understanding.

Sandy Liarakos:
Thank you. Just a point of clarification, I know you indicated diabetes as a pre-existing condition, can you clarify is that type 1 or type 2 or both?

Ron Evans:
With pancreatic cancer, it’s type 2.

Sandy Liarakos:
Type 2, okay. Thank you. This person asked: How would a person engage in clinical trials? Is that something where… What’s the process? I know you shared the slide of working with health centers all over the world, but if someone contacts you and they’ve been diagnosed with pancreatic cancer, how would they engage and enroll in a clinical trial?

Ron Evans:
Well, I get contacted all the time. I have a couple of pages of information on trials, the kind of work that we have, the first things you should do, to begin to put a team together to try to understand what’s going on. It’s very hard for the patient themselves to understand what’s going on because of the fog that you get when you’re diagnosed with a major illness. You need to get help from others. Trials are out there. We do link people to trials that we’re doing. You can go on the internet, actually, at clinicaltrials.gov and look up trials. You can type in pancreatic cancer. It’s good to go to get advice at a major cancer center, a hospital where there is research going on, that’s sponsored at the cancer center level, which means this is one of the elite hospitals. That’s where you can begin to get access to new, cutting edge therapies and, in many cases, getting on clinical trials. All of the major medical centers have trials going on. That’s, therefore, a good place to be.

Many of them are doing different trials. Some of them… Like in our cases, even though we’re running, you saw all the places that we’re working with, they’re not all running the same trials. We have four different trials with our partners. They’re different choices to be made, depending on the nature of the cancer, how advanced it is, the shape that you’re in, what you can take or not take. There’s lots of features that come into that. Keep in mind, a trial, you have to qualify. The other part of the trial is you may not know if you’re getting the drug or not. That’s the only way that we can progress forward, is doing trials. That’s been the fastest way to go for most diseases.

Sandy Liarakos:
Great. We do have a question from somebody who was just recently diagnosed with stage one. He’s interested in hearing more about the physicians that you work with. I gave him my e-mail address and we’re going to do that offline to give him those resources.

Ron Evans:
I’d be happy to work with anyone to get them connected to the best people.

Sandy Liarakos:
Thank you.

Ron Evans:
That’s one of the few things that I can do. I know who are the best people and they’re usually very open to talking to patients.

Sandy Liarakos:
Thank you. That’s very kind of you, thank you. We’ll make sure that we connect this gentlemen with you. The question: If you were diagnosed tomorrow, Ron, what is your advice for finding the right treatment?

Ron Evans:
Well, you have to get good advisors. You have to get a group of people working with you, that can first… Most commonly, people will want to go to the nearest major hospital to them. It’s been shown that that often is the best, in terms of therapy because if you have to travel or go to another state, it is harder. Now, if you have to travel and go to another state to get somebody special, you go. You shouldn’t make that to be the barrier. Many people do travel, to get therapy, especially if its only being done in a few places. That’s something to keep in mind. If you’re willing to do that, then that opens up a few other extra opportunities. It’s really something that comes down to being personal, the appropriate way to go or not. There’s no right or wrong answer here.

You do want to seek out, as fast as you can, this is a rapidly moving disease. You do not want to waste time on treating this. The way to do that is to assemble a group of people that can help you both find the right clinical center, the right doctors to get in touch with, and move quickly to be evaluated as soon as possible at some of the best places. That’s what I would do.

Sandy Liarakos:
Mm-hmm (affirmative). Yeah, that’s excellent advice. Here in San Diego, Southern California, we’re really blessed with many national cancer, NCI, cancer centers, but I know some of the people that are on this program today, are from all over the country. Really going on the NCI website, or contacting us, because Ron and the whole team here, have relationships with other cancer centers, NCI cancer centers. I think that’s all the questions that we have. I know, as a follow up, we’re going to be sending of course the link to today’s recording the vitamin D information, the video of Dr. Bigelson’s story and so if there’s any other resources that people are interested in, please contact me. Before we wrap up, Ron, do you have any kind of final thoughts?

Ron Evans:
Well, as I mentioned before, we are really building an incredible program here. We have some of the best talent and we’re in an environment that’s known for the kind of state of the art, leading, research that has translational relevance and so I do encourage you to think about, if you still wish to consider a donation, it would go a long way to helping the trials be analyzed, because that’s one of the most important ways to get information. As I’ve said, there’s a lot of information in every patient. Most of that information isn’t captured. This is the key. We are able now to capture this information, and each patient for us, is very relevant and very important. It also needs the support to be able to make that into a reality. You out there, can make this program really be significantly better and more impactful, by any contribution, because that will have a great impact for all of us. It’s greatly appreciated, whatever happens. I understand. I’m happy that you’re there to listen to this, and see the kind of stuff that’s going on at the Salk Institute.

Sandy Liarakos:
Great. Thank you Ron, and thank you to everybody on this program. We thank you for your support at the Salk Institute and the Power of Science. We are reminded, more than ever before about the promise and the hope we have in biomedical research and the impact on human health. Thank you all and take care.
Ron Evans:
Thank you.