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Alicia Morgans: Hi, I'm so excited to be here with Dr. Leanne Burnham, who is visiting us to talk about her 2020 Young Investigator Award with the Prostate Cancer Foundation. Thank you so much for being here.

Leanne Woods-Burnham: Yes, thanks for having me.

Alicia Morgans: Well, wonderful. So Leanne, please tell us, what was your project? What got PCF so excited about funding you?

Leanne Woods-Burnham: So my project looks at prostate cancer health disparities. We know it's not a secret that black men are more likely to be diagnosed with prostate cancer younger, they tend to present to the clinic with more advanced disease, and so any sort of project or research design that can sort of tackle that issue is important. And I was excited that PCF recognizes that. And so my project looks at HER2 expression and also a little bit of androgen receptor signaling, but as it pertains to black men in particular and then in comparison with men of other races and ethnicities. And so the project started when I was at City of Hope and has been conducted under the mentorship of Dr. Rick Kittles, who's on the scientific end of mentoring, and then Dr. Tanya Dorff, who is on the clinical side of mentoring. So I really have a strong team of leadership that sort of helped me develop the project and get it to the point that it is today.

When I developed this project, I met with Dr. Dorff because, for me, if I'm doing something at the bench, it's important to me that a decade from now when there has a potential to be in the clinic as a clinical trial, that it makes sense. Otherwise, I don't want to start it if it's not going to make sense for patients in the future. And so I met with her and she was able to be encouraging and say, "This absolutely makes sense. It sounds like you're onto something. Let's pursue this and see where it goes."

Alicia Morgans: Wonderful. And clearly, the Prostate Cancer Foundation agreed with her, and you've been working on this for about the last two years.

Leanne Woods-Burnham: Yes.

Alicia Morgans: Let me know. What have you finished?

Leanne Woods-Burnham: Okay. So this project is multifaceted. We have found that HER2 expression seems to be linked and positively correlated with West African ancestry. So why is this important? Well, African Americans tend to have their ancestry derived from the West African coast just because of the history of the United States and the Transatlantic slave trade. And so most African Americans have an abundance of West African ancestry, so what we saw was it just wasn't enough for self-reported race. So a patient saying, "I'm African American," that wasn't necessarily making that patient more likely to express HER2. But black patients that had a higher West African proportion in their genetic ancestry, that ancestry link seems to be tied to HER2 expression.

And so what we've done so far is using tumor tissue and performing RNA sequencing on the tumor tissue, the first thing that we see is that HER2 is correlated with West African ancestry. And so then we have a basic science project where we have cell lines in the lab. So we have African American cell lines and then European American cell lines, and we're able to, first of all, treat the cells with an anti-HER2 drug. So right now we're using trastuzumab, which is a little bit of an old fashioned drug, but we know that it targets HER2 directly. And so we've seen that when we treat the black cell lines or the white cell lines, that that drug is able to reduce HER2 expression, reduce cell viability in the black cell lines specifically. We don't see that effect in the white cell lines.

The other thing that we've seen we are going to be doing next actually, is we're going to be able to express HER2 in the cell lines and see what sort of effect that will have. So that remains to be seen, but we're going to be looking at cell viability first of all. But then we want to know if colonies are able to form, when we modulate HER2 how does that affect the migration of the cells. So that's the cellular work, but then we also have access to patient samples. We have about 800 patient samples, some from black patients, some from white patients, and we are performing immunohistochemistry staining to see, first of all, how strong is the HER2 signal at the protein level. And then we have access to clinical variables, so we'll be able to compare HER2 expression with Gleason score, PSA, or what treatments has this patient had, what was the overall survival of this patient? So we'll be able to link that. And at the same time, also perform ancestry genotyping, which looks at a set of SNPs that we call ancestry informative markers.

These are validated sets that anyone can look up in literature and see how we do that analysis. But basically, we'll be able to relate the HER2 with the clinical variables with West African ancestry proportion. And so that's what we are currently working on in the project.

Alicia Morgans: Wonderful. That's so exciting. And I wonder, has there been a clear link defined, and it sounds like this may be part of your next steps with your cell lines, between HER2 and driving cancer cell growth or metastatic disease? As you mentioned, it sounds like you're looking at metastatic assays certainly-

Leanne Woods-Burnham: Sure.

Alicia Morgans: ... but is this a driver or is this just something that's expressed on these cells?

Leanne Woods-Burnham: So I'm glad that you asked that. So HER2 expression is okay and normal to a certain extent as long as it's not overexpressed. And so HER2 tends to be overexpressed, and then it amplifies oncogenic signaling in the cell. And this, we know from looking at breast cancer and earlier prostate cancer studies, that HER2 over expression tends to occur in response to treatment, so in response to radiation or in response to chemotherapy or hormone therapy. What was interesting in our study is that we see HER2 overexpression in black patients who've never had any treatments yet. And so that sort of had a light bulb go off in us because HER2 has been associated with metastatic, treatment-resistant disease, but we're seeing it in a population where that's occurring earlier than that. So we really don't know the why or the how, so that's what we're working on.

Alicia Morgans: It's extremely rich to dig into all of this. And to your point, I have not heard about this really being demonstrated to be different by race and by ancestry even more importantly, so this is so exciting. What do the next couple of years hold for you, and where do you take this in terms of your next steps? Because your Young Investigator Award is really just a first step, right?

Leanne Woods-Burnham: Yes. And so I have recently transitioned to Morehouse School of Medicine and Prostate Cancer Foundation is still supporting this project during this transition, and I still have the mentorship of the clinicians at City of Hope on this project. The next steps, we have attained IRB approval to secure serum samples, whole blood samples actually, from prostate cancer patients that have metastatic disease. And with that blood, we are collaborating with Dr. Peter Kuhn at the University of Southern California, who is the master of isolating and characterizing circulating tumor cells. So with those circulating tumor cells, we will be able to characterize them and look at amplification of ERBB2, which encodes for HER2, but we're also going to look at amplification of androgen receptor and see if there's any correlation with prostate cancer genomics.

We don't know what to expect. So we are going to see though, when you have these patients that have HER2 amplified or androgen receptor amplified, what does that genomic landscape look like? And so that's in the immediate next two years on this project.

Alicia Morgans: Well, I am extremely excited to hear about where this goes. And congratulations on your award. Congratulations on all the effort that you've already put into this work. And I, as I said, really can't wait to see where your work takes us. Thank you so much.

Leanne Woods-Burnham: Thank you.