The Power of Science
Lecture Series

Reuben Shaw:
Hello, everybody. Welcome to the Salk’s Conquering Cancer in the Time of COVID Webinar. We are working through some behind-the-scenes technical details. And I just want to thank all of you for taking the time today to be here with us. This is obviously a stressful and a unique, incredible, time that we’re all living through with the coronavirus pandemic. And that is the top of everyone’s mind at this time. So I particularly want to start by thanking you for giving us your time today.

In just a minute, Sandy Liarakos, our fearless leader, is going to be explaining how the webinar is going to technically work, some of the rules of engagement as it were, and how people can type in questions through the use of the chat function within Zoom. Hopefully, all of you have had an okay time to get to the stage where you can see me talking as you hopefully do now.

I am coming to you live from the, not the Ed Sullivan Theater, but from my office, my study at Salk Institute. It is remarkable to be here at this time when all of life is closed down and even the Salk is quite shut down as I’ll speak to a little bit later. But it’s also important to remember the sun and the ocean and that life is going to go on and it is going to get better for all of us.

And in the meantime, here at Salk, we continue to fight the good fight of cancer research, and still have major efforts underway between ourselves, with our labs, as well as with our collaborators around the country. I think while we’re waiting for Sandy, I’m going to just go ahead and keep telling you about some of the things that we have going on here.

Coming back to the pandemic itself, it’s on everyone’s mind, there’s no way to escape the circumstances rend, but here at Salk, we remain dedicated in our momentum to make progress against cancer, which an ancient and terrible disease in its own right. One aspect of people who are undergoing cancer treatment right now is that they are at a unique risk, some of them, for COVID-19 as well as any particular infectious agents. So being vigilant with all of our clinical colleagues is top of the mind for the cancer community at this time. Oh, I see Sandy.

Sandy Liarakos:
Thank you. We had some technical challenges, but we are on. So, apologies for the delay. Welcome, everybody. Thank you so much for joining us today. Welcome to the Salk Institutes virtual presentation on Conquering Cancer in the Time of COVID-19. This is the first of these programs, so thank you in advance for being a part of this launch and this debut. And we welcome your feedback after the program today.

My name is Sandy Liarakos, and I’m the senior director of external relations in the Salk Cancer Center here at Salk. And I’m pleased to be the moderator for today’s virtual event. We recognize that today, April 22nd, was the originally scheduled date for our Conquering Cancer summit, which unfortunately had to be rescheduled. And we’re grateful to each of you today for taking time out to spend the next hour with us, learn about the Salk Cancer Center and hear firsthand from Dr. Reuben Shaw and Dr. Dannie Engle.

We’re excited to share these updates regarding the status of the research labs here at the Salk Institute, ongoing scientific collaborations, and of course the latest in cancer research. To lead off today’s event, we first wanted to share a message from Dr. Rusty Gage, our president of the Salk Institute.

Rusty Gage:
Hi, everyone. I hope you’re well and safe and finding ways to keep yourself happy and positive. Thank you for joining us in this digital event. We’re all adjusting to this new normalcy where we’re finding new and creative ways to keep connected with each other. Now, more than ever, I think we understand the importance of basic science. Because basic science is that which provides the foundation for understanding.

And this is a time where we need that understanding to solve this problem and this pandemic that is plaguing us. Most of all, I want to express my sincere appreciation for your support for the Salk Institute. I wish you good health. And I look forward to seeing you here on campus and the not too distant future. Take care everybody.

Sandy Liarakos:
Great. That’s wonderful. So after the presentation today, we’re going to have an interactive Q&A. We hope that you’ll participate. You are all muted right now and that’s on purpose and we cannot see you. So we’ll have a dedicated time after the presentation to have questions and answers. At the bottom of your screen, on the bar, is a place for you to submit your questions. If you have a question for Reuben or Dannie, please enter it there throughout the program. And we’ll gather those for the end of the program to go over.

If you were having an issue or need a resource, please enter that in the chat box. So we are recording today’s program, and we’ll be sending that out to you later this afternoon, so that you can share it with family and friends. So now we look forward to hearing from our presenters and we want to thank Dannie and Reuben. They each came in today to the Salk, to their respective offices. We were a little concerned about the Wi-Fi connectivity at our homes. So that’s why they came in today. So thank you very much.

First, we’re going to start with Dr. Reuben Shaw, who in addition to serving as the director of the Salk Cancer Center, is a professor in molecular and cell biology and holder of the William R. Brody Chair. Reuben studies the link between tumors and cellular metabolism and has made many important advances and discoveries in this area. In recognition of his extraordinary talent, Reuben received the outstanding Investigator Award from the National Cancer Institute in 2017

We also have with us Dr. Danielle Engle, and she is a graduate of Northwestern University where she completed her bachelor’s in Biology and Asian Studies. And then to UC San Diego, where she earned her PhD. Dannie was a PhD student in Jeff Wall’s Lab here at Salk before leaving us for the Cambridge Research Institute in the United Kingdom, and Cold Spring Harbor in New York.

She is doing some incredible work using individualized modeling and advanced stem cell techniques to create more accurate representations of pancreatitis and pancreatic cancer, which she will be sharing about today. So I’m going to start with presenting the program. Reuben will start us off. Thank you.

Reuben Shaw:
All right. Hopefully, you can all hear me and if not someone at Salk will start waving their arms profusely. I want to return and just start by thanking Sandy, and Dannie, and all of you, for taking time this afternoon to be with us. As I was mentioning for those of you who might be joining us late, a major thing pressing on all of our minds at this time, of course, is the coronavirus pandemic and the tragic circumstances that we in this country and in the world find ourselves in. While that is ongoing, as Dr. Gage just said, never is it probably been so obvious to so many people in the United States how critical biomedical research is and what the impact is of not having active research and not having the infrastructure to actually fight diseases as they come up. They can obviously bring the country to its knees and worse.

At Salk, in our cancer center, we remain focused and dedicated to fighting cancer as cancer rates and people being diagnosed with cancer is not stopping simply because there’s a separate infectious disease running rampant around the globe. As I mentioned, with respect to any relationship between COVID-19 and cancer, one particular aspect of this infectious disease, which is also true of the flu and all kinds of infections, is that many cancer patients who are undergoing therapy, the therapies will leave them immuno-compromised because their immune system is weakened from the actual therapies itself, which will then make them susceptible to other kinds of infection.

That’s also true for people with a handful of other diseases, which you’ve probably heard about in the news. And as a result, we have to have extra care and vigilance for our cancer patients undergoing clinical trials. Coming back to where I left off and Sandy joined us, as you may know, or probably are aware of, Salk has a number of clinical collaborators. We work with clinicians and professors at UCSD San Diego Moores here in San Diego, but also with a number of key researchers and oncologists around the country. An important thing for you all to know is that all of our clinical collaborators, even in York, at Memorial Sloan Kettering, at the heart of the epicenter of this, their clinical trials are still ongoing in cancer. The fight against cancer does not stop simply because there’s a new battle front from a different disease.

Now, turning to life here in San Diego and to here. At the Salk, we are in what we technically are calling maintenance mode. What that means is all events and seminars are obviously postponed, or they’re done via Zoom, just like this one. So that started on March 20th. Even before that we had guidance, and people who were not actively doing experiments were encouraged to work from home. But on March 20th, we went into this particular mode. And then only a handful of individuals from any particular lab are allowed to be on campus.

And those individuals, which are deemed essential, are carrying on the work effectively of the entire research enterprise. In particular, there are kinds of studies that we do, but not just in cancer and in all kinds of diseases, where you maintain cell types or certain genetic modified organisms that are models of disease. And you need to obviously keep those alive and keep those maintained over time.

In other cases, in my own lab, we have ongoing therapeutic trials testing new cancer drugs in new combinations. The experiment itself takes a year. And we have multiple that are right in the middle, so you cannot stop those or else you lose multiple years of time. And so some of those studies are still ongoing. And so, 30 yards out the window and downstairs for me, there are individuals, handful in my lab, all of them practicing social distancing of course, wearing masks, but going about the business of science as we speak and as we talk.

In addition, most of the researchers are home, but the business of science continues in terms of writing grants, writing papers. And many labs will actually have lab meetings still, Zoom meetings, we have journal clubs. We even, occasionally, have happy hours to make sure that we as scientists are all still connected. Ironically, in some ways, I think because all travel and other things have been cut down, I have been on more conference calls and Zoom calls with my colleagues at Harvard, at Stanford, Yale. I’ve had calls like that this week, visual conference calls with all of those institutions just so far this week. So, science is very much alive and proactively going on.

Now I want to shift gears and talk a little bit about some of the efforts at Salk that you may have heard about in the news. One of our senior professors, Greg Lemke, has been on a number of TV stations or radio stations, talking about the parallels between Jonas Salk’s original discoveries leading to the polio vaccine and its early clinical trials, as well as the current state in what is going to be needed for us to have a COVID-19 vaccine-related clinical trials this year.

Another person who… I don’t know if you saw the story that this past Sunday. There was a very nice article in the San Diego Union Tribune talking about all different efforts that each of the research institutes on the MESA and our very own Janelle Ayres, who’s a professor here, who focuses on infectious disease. Janelle has some very interesting ideas of how a one’s body and immunity actually couples to fight off bad microbes and bad viruses, sometimes enlisting the help of good microbes. And she is really a thought leader in infectious disease in the country. So we’re psyched to have her here and her insights into COVID, as she works with others.

On top of that, there’s actually a handful of researchers in different labs here at Salk who are actively working on COVID-19 itself, often collaborating with key labs at UCSD and with Sanford Burnham-Prebys and with Scripps, working on specific aspects of the virus. In fact, our very own Tony Hunter, our British wizard who defeats cancer also has a small effort fighting COVID-19, which you may hear additional new stories about as they come up over the coming weeks. Sue Kaech, who’s an expert in immunity here, and Ron Evans who works on all kinds of diseases, also have very interesting leads in different agents from my own labs as well. But they’re all have promised to fight different aspects of COVID-19.

So I am very optimistic that researchers like ourselves, trained in different disciplines but in different institutions across the country, are rallying together more than we ever might really together to contribute individual pieces of research that are going to help to really defeat COVID-19 in the next 12 months. But of course, the public is not used to watching science or watching clinical trials in real-time. So this is going to be an educational process for the whole country. But stay tuned as we will continue to keep you updated on, not just the efforts here at Salk, but the efforts worldwide.

Okay. Another parallel that this, of course, hearkens back to is to Jonas Salk himself. Jonas’s work that led up to the discovery of the polio vaccine was really pioneering and unprecedented up to that point in history. But one thing I wanted to address that some people have asked me about, offline in my life, is the difference is, the virus that Jonas made was the virus itself, just he didn’t activate them to kill the virus. And there were risks, in fact issues with early clinical trials where the virus was not fully inactivated and therefore some individuals could get sick from this. This is like 50 years ago now, of course.

But, it’s important to know that all modern vaccine making does not work in that fashion anymore. Now, one has the full genetic code as we did of COVID two months ago. Now, all the vaccines that are going on, both in the U.S and worldwide, are based off of just one little piece, one gene out of a COVID-19, that we can make protein against and then raise an immune response to that. So, no one has to worry that any COVID-19 vaccine that will be rolled out, it’s not possible that you could catch COVID-19 from any modern vaccine that’s made.

Okay. One other point I wanna make is that our president, Rusty Gage, that you just heard, also had us as an institute gather up all our surplus PP, protective equipment, and personal protective equipment. And we donated that to local hospitals to do our part in the fight of our frontline healthcare workers. Many of whom are our friends and colleagues.

What I want to talk about now is some new ongoing efforts. I just want to briefly give you a flavor of some of the things we have had going on here at Salk in cancer. There are two exciting new team science efforts that have really come about in the past six months that have some exciting new results. And you’re going to hear more about one of them from Dannie Engle, our pancreatic cancer expert in just a minute. But a team composed of Tony Hunter, myself, Ron Evans, and Dannie, has really formally come together. Each of us having different therapeutic angles to attack pancreatic cancer.

You may remember, if you were able to join us, one year ago, we had our second Salk Conquering Cancer Summit featuring Patrick Swayze’s widow, Lisa. And we talked about the particular issues with pancreatic cancer. One of the main issues is that when the tumors are detected, it’s very late, and they’re refractory to most therapeutics. For a number of different specific scientific reasons, they are effectively resistant to therapies. Beyond that, even when you start to get any response, they rapidly develop additional therapeutic resistance. And so that is the major focus of this work, which we’re very excited to be attacking collectively in a new way as a team. And Dannie will say more in just a second.

The other thing I want to talk about is, we have an effort in colorectal cancer. Ron Evans lab, towards the end of last year, made a very exciting discovery about how diet modulates the risk for colorectal cancer. Ron is now teaming up with Sue Kaech and Ye Zheng, who are both card-carrying immunologists in studying how diet impacts the ability of the immune system to respond both to these things that drive colorectal cancer, but also to potential therapeutic interventions. So that is two exciting new things that we have going on.

Finally, one last note before we go to Dannie, in more of the hot-off, the press’ category. Many of you will know that Padres Pedal the Cause is an annual county-wide cycling event, which is a major philanthropic fundraiser for cancer research in San Diego County. And this Pedal the Cause event raises funds for the three NCI-Designated Cancer Centers that we’re very lucky to have three in our county. So that’s a UCSD Moores, Salk, and Sanford Burnham. It uniquely gives grants to a clinician who’s actively seeing patients, and then partners them with a researcher who’s doing some of the mechanistic work to lead to new therapies. And so in the past year, our Tony Hunter received one of these Pedal the Cause Awards to work with a clinician named Peter Sage who works at Rady Children’s Hospital.

Now, it turns out that neuroblastoma is the name of the third most frequent tumor type of children. And tragically, neuroblastoma is detected soon after babies are first born. So this is a horrible cancer that babies are born with. And it turns out that one of the new enzymes that Tony’s lab has focused on in the last two or three years is altered in a subset of those neuroblastomas. And Tony’s lab has a good idea and a good lead on how to develop therapeutics against it. And that’s something that they have received a new funding for from Pedal the Cause.

So those are the types of very direct getting new treatments and new insights into patients that these mechanisms are built for. And this is the kind of research, of course, that you watching this have come to expect from us here at Salk. And that we appreciate so greatly. So with that, I want to turn it over now to Danielle Engle, who is coming to us from her office, I guess about a hundred yards away from where I am right now. That said, I have not seen Dannie, nor anyone else on the call, so this is quite an interesting mystery we have in this call. Take it away, Dannie.

Danielle Engle:
Thank you so much Reuben for that kind introduction and to all of you for joining us today. I’m here in my office, in my lab, which I think you can see behind me, it’s all dark, very empty, which is highly unusual, but we continue to stay very connected. My lab, very similar to Reuben’s, is participating in weekly lab meetings and journal clubs. And we’re trying to use this time to also come up with creative, new ideas and to formulate them into testable hypotheses through grant writing workshops and so on and so forth.

And so we’re staying very virtually connected, but for my lab here we’re only doing the most essential of tasks so that everybody can continue to work from home. And so today, I’m going to talk to you about how we can intervene more meaningfully for pancreatic cancer patients. And this is a very tough disease. And so what I’m going to start off with is introducing you a little bit about the problem.

So pancreatic cancer is what we would consider to be a very aggressive malignancy. And by the time we are able to detect pancreatic cancer in patients, it’s at a very late stage. Most of these patients already have metastatic disease by the time they’re diagnosed. And so in this first graph on the left, you can see the annual incidence rate, basically how many people are diagnosed in the United States each year with pancreatic cancer, in this blue line.

Unfortunately, that blue line is very closely mimicked by the red line, which is the number of people that are dying every year. And because those two lines are basically overlapping, what that means is that within a year, almost every single person who’s diagnosed with pancreatic cancer will pass away. And that really tells you just how aggressive this is. The median survival for these patients is very short. And the five-year survival of these patients is only 10%.

On the right, it’s actually showing you that while pancreatic cancer is considered a rare malignancy, it is a significant public health problem. And this is due to two things. First of all, the incidence of pancreatic cancer is increasing. And this is likely due to a combination of multiple different factors from a more sedentary lifestyle to increases in obesity and diabetes. And so these increased incidents means that more people every year are dying from it.

At the same time, our therapeutic interventions, once patients are diagnosed with metastatic disease, don’t work very well. And that means that we’re not able to actually intervene in increasing patient outcomes very effectively. And the combination of these two factors means that within the next five to 10 years, pancreatic cancer will actually become the second leading cause of cancer-related death. And that means that more people will die from pancreatic cancer than either breast cancer or colorectal cancer, which are two much more common malignancies. And so that means that pancreatic cancer is a very pressing concern and critical unmet need in terms of how do we intervene effectively for these patients.

And so when I started in my lab, I wanted to focus on changing how we approach treating our pancreatic cancer patients. So right now, we treat them basically all the same. And so continuing on, what I wanted to do is find a way of modeling each patient’s unique tumors. And I do that by creating what we call an organoid model. An organoid is basically just a fancy term for a three-dimensional way of growing or propagating a person’s individual tumor.

And so what you see here in this tissue culture dish are these little dome-like structures of jelly-like material. And that jelly-like material gives these cells three dimensions to propagate in. And you might not think that this is rocket science, because we are three-dimensional beings. But it turns out that if you grow a patient’s tumor samples in this three-dimensional context, it’s much more meaningful.

And so these organoids are buried within those little domes, and you actually just tilt the plate up. You can actually see them with the naked eye. They are between one and three millimeters in diameter, and they look like little tiny bubbles or balloons within each of those domes. And so if we take a closer look and magnify the view of these organoids, you can see that within each of these domes are hundreds of these balloon-like structures. And each of those structures is an individual organoid.

From a single patient, what we try and do is rapidly propagate as many organoids as possible, as quickly as possible, so that we can test as many drugs as possible. And by doing these drug tests in a patient model, we’re hoping that we can actually predict which drugs a patient is more or less likely to respond to. And so right now that we just assign different chemotherapies to patients based on their statements and based off of an educated guess.

And so what if we could actually inform these decisions with data? Data from these models about how they respond to different chemotherapies. And so in the next slide, what I’m showing you is how these models respond to different treatments. And so in this graph, every single circle is a different patient’s model. And so we have about 68 different models in this graph.

And what you can see on the top section are models that are very resistant to this chemotherapy called gemcitabine. And gemcitabine is one of those very common chemotherapies that are given to pancreatic cancer patients. And so those models don’t respond to this drug. So what we would predict is that the patients are also very unlikely to respond to that drug. Instead, on the bottom, you can see a handful of patients in the blue. And these patient models are extremely sensitive to these drugs as organoids. And so what we would predict is that these patients are the most likely to have a very good response to these drugs. In other words, these drugs are the most likely to shrink those patient’s tumors.

And so what does this actually look like in terms of impacting clinical care? And so through a series of different retrospective studies, we actually compare whether or not these organoid models from patients would predict the clinical outcomes or drug responses in people. And so what we have here first on the left are the radiological scans, showing a large tumor in this patient’s pancreas. This is the top scan. And this patient had a two and a half centimeter mass in her pancreas.

Unfortunately, at the time of diagnosis, their cancer had already also spread to their liver, which is the bottom scan. She unfortunately had a five and an 11 millimeter lesions in her liver already. And so while we were making organoids from this patient, she went ahead and received what we call a standard of care regimen of two drugs in which there was really no response detected, as well as one drug which we predicted the model to be highly resistant.

And so, in about 150 days later, the patient went in for another scan. And unfortunately, in every single lesion, in every single tumor, it had advanced. Meaning that, either had doubled or had tripled in size. Using those two drugs that we considered not to be effective as well as one drug which we actually predicted to be highly resistant. So that’s one example of how the responses in the model were predictive.

At this point, the oncologist switched the patient to two drugs that we predicted this patient would be highly sensitive to. And what we found in 150 days later is that every single lesion had shrunk. And if we actually look long-term, several of the lesions in the liver completely melted away. And what this translated into for this patient is the dramatic increase in survival.

And so I think what’s important to realize is that when you’re diagnosed with metastatic pancreatic cancer, the median survival is only 180 days, which is barely anything at all. This patient, just by being put on the right chemotherapy as soon as possible, lived more than a thousand days. And so that is a dramatic increase in survival. And that time that we’re able to give these patients is very meaningful.

And so in the next slide, what I want to show you is an example of this happening at the Salk Institutes. This the first patient that my lab has tried to help since starting my lab last year. And so this is a patient that was diagnosed with stage four metastatic pancreatic cancer. She had more than 30 different lesions in her liver, so incredibly aggressive disease. What we were able to do is start up a very productive and a very synergistic collaboration with the Moores Cancer Center at UCSD, where I work with a scientist Herve Tiriac. And what we were able to do is get a small sample from a biopsy that was taken for her standard clinical care in late November. And within about two weeks, we had established a very prolific organoid culture that grew very rapidly, we were able to do drug testing very quickly.

And so what we were able to do in the next slide is actually show whether or not there’s any treatment response to the drugs that are commonly given to these patients. And the first thing that I want you to notice is that her organoid line is highlighted by this bright red dot. And it’s almost always in the red for these standard of care treatments.

And so looking at this, we would say that, in five of the cases, we would predict extraordinary resistance. And then the remaining three cases, just an average, no response to chemotherapy. And when you see something like this is very discouraging, but it’s actually extraordinarily common. So about one-third to half of the patients that we test do not have a response to any drug that is currently used for pancreatic cancer. So this is incredibly discouraging. And what do you do at this point? Do you give up? Do you tell the patient, sorry there’s nothing that we predict will work for you?

For us now, what we try and do is we try and extend our work to other drugs that are either used for other cancers or close to approval by the FDA. At the very least what we can do is, if we find something, apply for compassionate use from the FDA. Which is an agreement between the patient, the pharmaceutical company, and FDA, to try and experimental treatment when there’s no other option for a terminal disease. And so we did, over the course of the next several months, a test over 50 different single and cognitorial treatment strategies to try and come up with something that might work for this patient.

And so continuing on, what you can see is that we’re actually able to identify… This is an example of one of the three different agents that we found this patient was highly sensitive to. This drug is called selumetinib. It is not traditionally given to pancreatic cancer patients, but it can be given to patients with other types of cancer. And so what we found is that this patient was the seventh most sensitive that we have seen to this particular agent. And this is what hope looks like for a patient that has metastatic pancreas cancer and has exhausted all other drug opportunities.

And so what we’re able to do is, for a few of the different options that we found for this patient were able to actually request compassionate use from the FDA, negotiate provision of this drug for the pharmaceutical company. And the patient was actually able to receive it. Unfortunately, as I mentioned, this patient had 30 different metastasis in the liver. And within one week of receiving the new agent, passed away due to hepatic failure.

And so this is the harsh reality that we face, is that we need to be able to move faster. And while we had to test over 50 different compounds to identify three that worked for this patient, but we know now that we’ve seen this work before in patients in their patient models. And so it was just start with these agents earlier in the pipeline. We’re very disappointed that we weren’t able to help this patient, but we are able to learn so that we can move faster in the future.

And so what I want to do is just summarize quickly what I’ve shown you. And that is that, in retrospective settings, we’re able to demonstrate that these patient models called the organoids, you’ll predict response to therapy. And could be used identify new treatment strategies that might work for patients that are resistant to all other standards-of-care opportunities. And so what we’re working on now is a prospective clinical trial, where we actually use organoids to actively change a patient’s treatment strategy. And this is being carried out by Cold Spring Harbor through a collaboration and funding with the Lustgarten Foundation. And so I hope that within the next five years, this might actually turn into an FDA-approved test that we can roll out for all pancreatic cancer patients.

In the meantime, what we’re trying to do is figure out how can we move faster. So it took us seven weeks to come up with the initial drug testing result for this organoid panel. And honestly, that’s not fast enough, or we’re not satisfied with how nimble we are in the laboratory. So how can we improve this? And so we are currently looking for different biomarkers that will predict a patient’s response without needing to actually do the empirical drug test.

At the same time, if you attended our previous seminars and events, we always talked about the fibrotic scar tissue that is present in a pancreatic cancer. And that fibrotic scar tissue, it actually protects the tumor cells from the treatment that you’re trying to give the patient, and actively impedes the drug delivery to the tumor. And so really, once we actually move from a treatment in an organoid model to a patient, it becomes much more difficult. And so we might actually under or overestimate the effects of the drugs that we’re testing. And so what we’re doing is actually incorporating that fibrotic scar tissue into the drug testing pipeline so that we can improve the accuracy of the test.

And I wouldn’t be able to do any of this work without some amazing collaborators and my team. And so since having my lab open for about just a year and a few months, I’ve been able to recruit a lot of hungry people that really want to make a difference for pancreatic cancer patients. And so I really want to thank that the two people in the middle of this photo, Jan and Sejin. They’re my first two postdocs. When we get a patient sample in the lab, they drop everything else that they’re doing so that they can focus fully and moving as fast as possible to come up with a different treatment options for these patients.

And so that is not good for their career, I want to point out. Instead, that is a very humane and ethical thing that we do because we recognize that helping our patients is the number one priority. And they are also continuing to maintain some very fragile organoid cultures in the lab that aren’t ready to be cryo-preserved and are at very fragile states. And so they are continuing to come in to support those tasks as essential so we don’t lose any models that were generated from patients, because that would be quite devastating for their care.

I was also able to recruit two people right before the labs shut down. So I’m welcoming my third postdoc, Jake, as well as my technician team, Sasha and Kristina. Again, like the Salk and the MESA is incredibly collaborative. So we work very closely with the Department of Surgery at UCSD with Herve Tiriac, specifically. And I do want to say that we couldn’t do this without your tremendous support.

And I do want especially thank the Emerald Foundation, as well as Larry and Carol Greenfield, for believing in my lab as I first found my feet and got started. And so I think that I’m starting this research endeavor is quite important for our patients, but more difficult to fund through the traditional networks. So I want to say thank you to you all for your attention. And I think we’re going to move now another update from Reuben.

Reuben Shaw:
Great. That’s so great. Thank you, Dannie. It’s really exciting to hear how the research in your lab is directly testing and leading to therapeutic options in real-time for patients diagnosed with cancer right now. That is the kind of thing, that combination of clinical collaboration and coupling that to cutting-edge research, that is really the heart to me of what we do here at Salk and what we try to do. And that’s what keeps us going. Now we’re going to take cancer down, even one patient at a time until we eradicate this horrible disease.

Now, I just want to wrap up here by talking about some of the larger things that we have going on in Salk Cancer Center. In particular, we have some very interesting progress and cool things with our Conquering Cancer Initiative. Exciting, albeit disrupted a little bit or a lot by COVID-19. But that’s okay. One of the exciting new things that we were just about to launch, it was basically about to happen, is that we have a brand new seminar series called Bench-to-Bedside-to-Bench that we’re very excited to announce. And this is due to generous funding from Sue and David Mendell, as well as many people to the Conquering Cancer Initiative. We were able to plan and just about to have our inaugural launch event for the seminar series.

This is a unique opportunity where we bring in clinician scientists who are on the cutting-edge of the latest and greatest therapeutics within an individual type of cancer. And we have them give a talk here. This is a draw, not only for Salk scientists, or Salk plus UCSD or Burnham, but actually we expect and have anticipated people from around Southern California will seek out this event. As there’s nothing else quite like it, where you have such a direct and proactive mixing of the research scientists with the clinicians.

We had our first event that we had to postpone, we have a highly-impactful physician scientists from UCSF scheduled to come down and kick off our first event. So we will postpone that until the fall, hopefully. But this is a very high priority, and I just want to thank all of you for being a part of that. And particularly David and Sue.

In addition, we have a number of other existing and important critical things going on within the Salk Cancer Center. Just prior to the COVID-19 shut down, we had actually been interviewing a number of top candidates in cancer research from around the country. And have two different candidates that are leading experts in different aspects of cancer research that I don’t want to spoil it by saying too much, but knock on wood, there are going to be two new fresh faces of young assistant professors focused on different types of cancer, who you will be able to meet with us in the coming year here at the Salk Cancer Center.

Finally, we also have some other new exciting papers that are coming out on cancer research. There’s a paper just out from Jeff Wall’s lab on an aspect of a type of cell contributing to pancreatic cancer. And there are other papers upcoming from a number of our labs. You can look for all of those advances in emails and things that come out from us. But again, let me just thank all of you for taking your time to be with us today. Before I turn it back to Sandy, I just want to thank you and encourage you to stay safe, to stay sane, and to keep fighting cancer. Thank you.

Sandy Liarakos:
Briefly, the philanthropic impact, we understand that COVID-19 of course is a major focus, but we want to assure our partners and our donors, our stakeholders, that the mission of cancer research continues. And we’re incredibly grateful to our funders, the foundations and grantors who have shared with us over the last several weeks, that they are being flexible on grant terms and providing extensions during this time, which we’re incredibly grateful for. And we appreciate hearing from donors whose passion for cancer research is even more determined at this time.

I think one thing that this pandemic has really been a great reminder of the strength of biomedical research and the foundational science is so critical. So philanthropy is the catalyst for discoveries, new treatments, new drugs, new vaccines. And as Reuben and Dannie have shared, this important research continues. And we continue to work to identify new supporters. So if you have ideas for people that we can reach out to, who are interested in cancer research and our projects here at Salk please let us know.

And we do have a deep appreciation for each of you on the call for your involvement, for your dedication and your partnership with our efforts. We always enjoy sharing with our supporters the impact that their support and their gift has had on the research here. So now, we’re going to go into our Q&A. And we’re going to begin that. We have already a few questions from folks, but I do want to give us the opportunity over the next, say, 15 minutes or so to go through questions.

If you would like to share your video or your audio, if you’d like to be seen, you need to raise your hand at the bottom of the screen now, and then our technical coordinator, Mike, will restart your connection to give you access to the video so that you’re able to ask your question, either audio or through video. I do have four questions here already from Eve and Heather and Dr. Greenfield. So I will go through those now, but if you would like to ask a question live and either again be seen or through audio, please raise your hand now and Mike will bring you up to the panel here.

So we’re going start. Eve has asked a question to you Dannie, to share a little bit more about the compassionate use with the drugs that you had shared about briefly. Could you just share a little bit more about when that applies and when it doesn’t.

Danielle Engle:
Sure thing. I think this is something that has to be decided between a patient and their doctor to figure out whether or not the potential benefit outweighs the harm. And this becomes more appropriate when a patient has failed the current treatment strategies for pancreatic cancer. So when chemotherapy stops working, there’s really nothing else that’s approved for pancreatic cancer treatment. And so if there is any data whatsoever that suggests that the patient might benefit from experimental agents, they can actually apply to the FDA for compassionate use. And that relies on the patient and the doctor thinking that this is a good idea, as well as the pharmaceutical company being willing to provide that drug to the patient.

And so this is something that requires that you are juggling several different balls in the air. So it is a little bit complicated. And there’s also, quite honestly, a significant financial burden associated with it since these experimental agents are not approved, they’re not usually covered by insurance. So several different considerations have to go into making the decision about whether or not compassionate use for a certain drug is a good option for a patient. Especially because that means that there’s no clinical data, no clinical trial currently being run for that drug, or that would suggest that that should become standard of care for these patients.

Sandy Liarakos:
Great. Thank you. I’m going to ask one more question then we actually have… Susan has going to ask another question. Dr. Greenfield asked a great question. In regards to COVID-19 which has RNA as its genetic code, can any of the newer RNA silencing and blocking drugs help against COVID-19? Reuben, I’m hoping that you can take this question.

Reuben Shaw:
Yeah. That’s a great question. It’s a great point. And the short answer is that people certainly hope so. That is the type of approach that some companies, including even some local companies, are taking. The good news about what we know about COVID so far is that it is similar to previous corona viruses like SARS and MERS which didn’t impact us here in America nearly as much. And we know a lot about different ways to attack those, short of a full vaccine. But you’re absolutely right, Larry, that this is an RNA-containing virus. And methods to extract and target RNA, of which that is a whole specific type of therapeutic approaches, may be effective. And that is something very actively being examined. So, good idea. Good point.

Sandy Liarakos:
Great. Thank you. We’re going to first, next go to a question from Susan and then Rosalyn and then Heather. Susan, go ahead with your question.

Susan:
Oh, yes. Well, first of all, I’d like to say how much I respect and appreciate what all of you do. I think it’s very, very encouraging and inspiring. But my question, I think, is for Danielle, perhaps because she said… I thought she said that there was a communication between surgery or oncology maybe at UCSD and Salk. And I’m wondering, how are the results and the outcomes that you discover shared with all healthcare institutions in the county or perhaps in the world? And how quickly does that happen after you discover something through your collaboration with UCSD?

Danielle Engle:
That’s a great question. There are a few different mechanisms where we keep this collaboration between foundational knowledge, like the research that we conduct here at the Salk with the clinicians nation and worldwide. And so what we like to do is go to conferences and meetings and present our work even before it’s published. Once it becomes published, we try to disseminate that knowledge as fast as possible through additional meetings and conferences.

But what really drew me to San Diego and to the Salk is that people here are incredibly collaborative. I now have interactions with the UCSD with their cancer center and their Department of Surgery on a weekly basis. And so what we try and do is as soon as we think that we have something that is interesting, we try reaching out to different clinical collaborators to see if they think it’s a good idea, and to see what they think that we still have to do research-wise to test it before moving it into clinical trial.

And so what we try and do is stay very engaged with our colleagues and disseminate our results even before they become published so that we can move as quickly as possible. And so I think publications and meetings and conference, those are kind of what we read at night once we get home after dinner to make sure that we’re staying up-to-date.

Once they actually become finalized in terms of becoming FDA-approved through clinical trials, there’s an update to what we call the national guidelines. And those national guidelines are then distributed to all of the oncologists that treat pancreatic cancer patients so they know that the standard of care has been updated or changed. And so that’s kind of how we keep this whole entire network coordinated so that everybody is making progress at the same time.

Sandy Liarakos:
Great. Thank you. A question from Heather she had asked for more information regarding the connection with COVID-19 and cancer. We know that with COVID, some of the symptoms have to do with respiratory or the respiratory system, and Reuben, maybe you could answer this, is there a connection with what this impact could be in lung cancer?

Reuben Shaw:
Yeah. Another good question. With COVID-19 or any severe viral infection, severe case of the flu as well, other viral infections where ultimately the lungs have scarring, often do if you have severe cases of pneumonia. So this would come into play certainly if patients need to be hospitalized and are intubated, if they have a kind of very advanced cases of COVID-19, it is likely that they may have some scarring. Anytime you have scarring or heavy pneumonia burden within the lung, you’ll have inflammation.

And there’s good research that demonstrates that those types of events are in fact do increase the risk for lung cancer in particular, because that’s where the site of the scars are. However, a good thing to bear in mind is that the elevated risk is not that much. It’s more of a 10 to 20% increased risk, not immediately, but over the course of one’s lifetime, going on to develop lung cancer. So that is a real long-term ramification for patients that have survived a severe COVID-19 battle. But that is something that can therefore be monitored more vigilantly than perhaps a person would normally be checking for lung cancer, they wouldn’t be checking for lung cancer. So because people have had severe COVID-19 cases, that would be a good thing to advise them to do.

For many people who have mild cases or asymptomatic, there is no reason, no reason at all that having COVID-19 ever should not change your cancer risk, for lung cancer or for anything else. It should not impact it at all. Same thing for SARS or H1N1 and for those particular types of respiratory viruses, they themselves are not directly causative for cancer. It’s more of the scarring if you had a bad case. Good question.

Sandy Liarakos:
Great. Thank you. And there was a question here from Rosalyn, who shared that she attended this Salk luncheon in New York in December and heard about a pancreatic cancer who was in remission after taking large doses of vitamin D. Has there been any progress with this treatment that both you can share about?

Danielle Engle:
Yeah, I can take this question. It’s a great question. It is something that was originally discovered by Ron Evans. And is now in clinical trials at multiple different sites. I think we still have to wait and see whether those results should be incorporated into standard of care. So the clinical trials are ongoing. They do think it’s important to point out that vitamin D, by itself, doesn’t really hit the cancer cells. It kind of targets that fibrotic scar tissue so that drugs are more effectively delivered to the tumor cells.

And so right now, it’s being evaluated in combination with other chemotherapies and targeted agents to figure out does it potentiate other drugs that we commonly use for pancreatic cancer, or does it make, for example, immune checkpoint blockade or immunotherapy, which traditionally has failed for pancreatic cancer. Does it actually increase the response rate in pancreatic cancer patients?

And so I think the reality here is that those results we discussed last year in the clinical trials have been ongoing, I think, for two years. But traditionally, these trials take at least five years to complete because they do require first, safety and efficacy studies. And so we go through a phased clinical trial process where the first stage is just making sure that we don’t make things worse by giving this drug to patients, making sure that we understand the side effects so that if we cause any of them in these patients, we’re prepared to treat them accordingly.

Then it moves into kind of these phase two trials that are smaller that’ll test whether or not it improves survival in a small cohort of pancreatic cancer patients. And then finally, you’ll see phase three trials usually involve hundreds to thousands of patients to see, in a broad multicenter approach, does it reliably and robustly increase survival? And so this process, I would say for certain types of cancer, can certainly occur within five years. But for a rare type of cancer, like pancreatic cancer, we’re looking actually at five to 10 years before it gets incorporated with the standard of care.

So I think we still have some time to look for updates, but there will be… We have annual meetings, it’s called ASCO, where we look at the progress updates from these clinical trials. So we can start to look the preliminary data coming from them. So we should have an update from this big ASCO meeting once we know what’s going to happen to it in the current pandemic. And so I think we should have updates that Ron is probably the best qualified to speak to at our next Conquering Cancer Initiative event.

Sandy Liarakos:
Great. Thank you. I think we have time for just two more questions that have been waiting. One is from Susan Mendell. When a vaccine is developed, what happens if the disease mutates? And how does the vaccine still work? I’m assuming that she’s maybe referring to COVID or maybe another vaccine. Reuben, can you take this one?

Reuben Shaw:
Sure. Part of it depends on the actual details of where the mutations occur within the viral genome sequences and how central to the portions of the viral genome that were used for the vaccine any mutations are. In a way, you would almost have to get horribly unlucky that the virus would mutate in the direct place that the vaccine was made against. What’s more frequent, and all of us probably have some exposure to, is you hear that certain years, “Oh yeah, the flu vaccine wasn’t very good this year.” “Yeah. I heard that. I heard the flu vaccine wasn’t very good this year. I guess they got the mismatch was off a little bit.”

What that functionally means is that the vaccine, scientists are guessing or taking sequences. In that case often from Asia as well, where the new influenza viruses are coming out. Sequencing them and making vaccines against those sequences is, over the course of literally a calendar year, in the case of influenza, the sequences will change a little bit. But not enough that makes the vaccine worthless, it just makes it 60% effective instead of 95% effective.

I am not an expert enough on the details of how rapidly coronavirus can mutate. My understanding is that it’s less than influenza. So from the health expert’s infectious disease and virus virologists that I’ve been hearing from, my understanding is that the odds of an early COVID-19 vaccine holding true would very likely be the case for at least a year or two. And the odds of the vaccine mutating around even one particular cocktail, that’s the other thing, is that scientists will deliberately make vaccines against three different sections or something of the viral genome, to deliberately not box themselves into a corner where if one particular bit of the virus gets lucky and just mutates around the vaccine, then you’re in trouble.

That is of course what happens with cancer therapeutics, the tumors. Just like the viruses, the tumors actually mutate around the therapeutics that we give them. And because the cancer therapeutics are often based around one particular protein, one particular region, it therefore, depending on what type of therapy you’re using, it can actually be relatively quick for the tumor to mutate around whatever therapy you give it.

So just like my analogy here with the vaccine, most effective cancer therapies, not all, some can lucky and a single drug will do it. But usually, you need to come in with a cocktail against three different types of drugs, or three different targets. Same thing then with the vaccine, you want at least three different parts of COVID-19. But I’ll expect that’s what will happen.

Another thing is that many different companies, and hospitals, and research labs, are making their own different COVID-19 vaccines. So the other good news is that the world is probably going to have 10 to 20 different COVID-19 vaccines that will be tested. It may take two years before we all discover which one is really the best one, but I have great faith in our biomedical science system here in the States, as well as worldwide. Scientists are certainly used to working together all the time across borders. And we will continue to, to fight the disease. No matter what else is going on, we’re going to fight it. That’s what we do. Thanks.

Sandy Liarakos:
Right. Thanks for Reuben. We want to honor everybody’s time. It’s a few minutes after three. We want to thank you, Dannie and Reuben, for providing today’s platform to learn more about the cancer research that’s going on. And to all of you on this call, we thank you so much. We want to extend the learning and connection during this time. And we look forward to inviting you providing additional information. We will be doing that today with the follow-up link to this recording, as well as other links to some of the articles and papers that Reuben and Dannie were referring to. And we look forward to hearing your feedback, your ideas.

And if you are interested in attending future programs, this was the first. And we thank you for being part of the first. And we look forward to having other programs in the month of May and June, and we hope that you’ll be involved. We look forward to hearing from you. Thank you very much. We’re grateful for you. At this time, we’re going to wrap it up. Thank you all for being here. Take care.

Reuben Shaw:
Thank you.