Alicia Morgans: Hi, I'm so excited to be here with Dr. Isla Garraway, who's a Professor of Urology. Thank you so much for being here, both the clinician and running your own lab, which is just so exciting.

Isla Garraway: Thank you so much for having me. It's a pleasure to be here.

Alicia Morgans: It is always wonderful to talk to you, Isla. I really wanted to talk with you about some really cool initiatives that are happening to engage researchers with the VA system. And then also, of course, we want to focus on how you're using this to really leverage it in your lab work today. But let's start with the program that a team has put together, you included, to really link researchers, not just in the VA, across the spectrum with patients and samples from the VA.

Isla Garraway: Oh my gosh. Well, I'm always happy to talk about VA research. It's very exciting. The Prostate Cancer Foundation made a huge commitment to supporting VA research and not only VA research, but just really making sure our veterans had access to the same precision oncology medications and clinical trials that anybody else in any wonderful academic setting that they support would also have access to. They made a huge commitment to fund different components of the VA Care Program. As part of that, they formed a prostate cancer network of investigators who are both within the VA as clinicians and providers, but also have affiliations with academic institutions, like in my case it's UCLA. But we formed this wonderful network and one of our first priorities was actually to really leverage the diverse population of veterans who had been diagnosed and treated within the VA system for prostate cancer.

To do that, we formed a biorepository that includes both tissue specimens as well as data from these patients, because of course, we all know that the Veterans Health Administration was one of the first to institute an electronic medical record system. A lot of data can be housed in these corporate data warehouses where we can get all these elements of the patient's natural history of prostate cancer, what treatments they had, what imaging they had, what their whole cancer course was like. We have now established this study that anyone in our POPCaP network can apply to, and anybody who wants to collaborate on, can join one of the investigators to do collaborative studies.

Alicia Morgans: Well, that is so powerful because as you said, it's not just samples. It's really all that data that's housed in the electronic medical record that gives a full picture and helps us understand even a longitudinal perspective on these patients. But one thing that you mentioned before we started talking on camera of course, was that this is not only a retrospective database, or at least this is augmented by potentially prospective enrollment of patients to further your understanding even more.

Isla Garraway: Yes and thank you for bringing that up. Yes, one essential component of this repository is that we did want to be able to collect specimens from patients who are at risk of prostate cancer. A patient coming in undergoing a biopsy who has a risk or suspicion of prostate cancer, we can consent them to participate in our study, so that potentially we could collect additional samples, if they're undergoing a biopsy, for example, and it's safe, and we can collect blood and urine and saliva samples from them as well. And then those can be stored in the biorepository for translational studies that are being proposed by our collaborative members.

Alicia Morgans: That's fantastic. And I just wonder if you could talk a little bit about the veterans population and how that population is unique and important for us to really investigate as some of the patients, at least in the Veterans Administration, are patients who have not been really fully characterized, included in clinical trials and really understood in the same way that some of other populations have been.

Isla Garraway: Yeah. The veterans population is a very special and very unique population. Obviously, we're so grateful to them because of the sacrifice they've made for our country. It's a very diverse population, which is amazing. They come from all parts of the country, from rural areas, from suburban areas, from urban areas, from all geographic locations. They are representative of so many different race and ethnicities, and they have very different social experiences as well, and we can learn all that information from them.

They are very eager and willing to participate in trials and studies. For example, there's the Million Veteran Program, which is an amazing study. Another by large repository effort to collect data on our veterans and learn more about their experiences, which gets lifestyle, nutritional data, family history, so all these data points can kind of be pulled together to have a much deeper understanding of the patient experience in the context of their disease.

Alicia Morgans: Well, this is incredibly powerful, and I know that you and your laboratory have been able to leverage some of these efforts to continue your work in your lab at UCLA. Can you talk a little bit about that?

Isla Garraway: Yeah, well, it's so rewarding to be able to actually put those specimens into use to try to further our understanding of cancer. Our laboratory at the Jonsson Comprehensive Cancer Center at UCLA, a lot of our studies have been supported from the get-go from Prostate Cancer Foundation, so we're just always grateful to them for their support. Our focus is metastatic prostate cancer and understanding biological factors that lead to their aggressive behavior. And so by using those specimens that we have collected from our veterans that are so highly annotated, we know who had high grade prostate cancer, but was able to achieve a cure, compared to unfortunately, those patients who did not achieve cure and had spread of their disease. We can compare those samples and understand the molecular differences, as well as some of the cell biology differences in our laboratory.

Alicia Morgans: Well, that's incredibly exciting. Is there anything that your team has published recently that you're willing to share?

Isla Garraway: Absolutely. One of the striking things that we noticed in patients with really high grade prostate cancer, the difference between those with high grade prostate cancer whose disease spread versus those who we were able to cure with surgery or radiation treatment, on the molecular level is how the integrity by which those cells were able to divide. When cells divide, their DNA separates and it really should be, you just have two exact copies of DNA in the cell. What happens when you have a really aggressive prostate cancer that is liable to spread is that the integrity of that process is really, really disrupted. It's called chromosomal instability. And so as a result, you end up piling up and accumulating all these genetic alterations and mutations in your DNA, which perhaps can lead to the aggressive nature of tumor cells because you have this whole heterogeneous population of tumor cells that can form with each division.

Alicia Morgans: And certainly that unequal divide leads to the buildup in some cells that, of course can then transform and spread.

Isla Garraway: Exactly. Yeah.

Alicia Morgans: So wonderful and so important and exciting that your laboratory is really defining this, showing us this, and hopefully giving us potential for new targets for therapeutics that can be developed in the future.

Isla Garraway: Well, we certainly hope so.

Alicia Morgans: Wonderful. Well, I just wanted to say thank you so much for your efforts in terms of really emphasizing the need for, and then creating this VA wide network, this biorepository that's not only retrospective, but also prospective, whereas you said, you can activate the members of this organization to really help you with prospective work. And then of course, for the work that you do in your laboratory, it is always exciting, and I'm sure that PCF and those of us in the community are just eager to see what you and your team are going to do next.

Isla Garraway: Thank you so much, Alicia, for the opportunity to share our work.