Steven Patierno, PhD, professor of medicine (Medical Oncology) and deputy director of the Duke Cancer Institute, studies the biological underpinnings of disparities in prostate cancer among African American and Caucasian men.
How did you get interested in disparities research?
Before I came to Duke, I was the director of the George Washington Cancer Institute, located in the heart of Washington, D.C. Leading a cancer center in a majority-minority city, I felt a moral imperative to address healthcare disparity issues. I wanted to address disparities both from a service perspective—providing programs and getting out into the community—but also with research. In prostate cancer, we began to notice that in studies of closed systems, like the military, where access and quality of care are equal, there were still big differences in mortality. A higher proportion of African American men were being diagnosed with later-stage disease and more aggressive disease. That suggested there might be some biological contribution.
How can there be biological health disparities related to race if race is not biological construct?
There are differences in genetic diversity as a function of the human diaspora. We are all out of Africa. The differences between our populations are a function of when and in which direction your ancestors left the African subcontinent. The diaspora generated genotypic diversity, and that diversity creates different susceptibilities to different diseases and different disease outcomes.
What have you discovered through your research?
When I was in D.C., we found a large number of differences in gene expression between prostate cancer in African Americans versus Caucasians. Our initial study was to sequence the genes showing dysregulation and look for mutations—we found nothing. So we did another type of study on those genes and identified at least 10 that undergo alternative splicing—where the genes produce several different variants of RNA. Those genes generate a different dominant splice variation in African Americans with prostate cancer compared to Caucasians. We cloned the splice variants from some of those genes and discovered that the dominant splice variant from African American men was contributing to increased aggressiveness of those tumors in vitro.
Might this lead to a therapy?
We’re working on a splice-switching oligonucleotide—a little piece of DNA-like material—to see if we can influence the splicing process. It’s all in the lab right now, but if we get positive data we would hope to move to a human study.
Would the drug be just for African Americans?
No, it would be a treatment for everybody with aggressive prostate cancer. By using population level differences between blacks and whites, we were able to fish out genes that drive aggressiveness. Those genes are disrupted in highly aggressive prostate cancer regardless of race.
How might your discoveries inform treatment decisions?
The biggest question is not who’s going to get prostate cancer—just about every man over 80 years is going to have it—the biggest question is who’s going to die from it? Who’s going to require surgery and hormone therapy and chemotherapy as opposed to active surveillance? We’re discovering biomarkers that help distinguish between aggressive and indolent tumors. That has all kinds of implications including medical economics. One major reason there are questions about overtreatment of prostate cancer is that we can’t tell who has the aggressive form so the default is to treat everybody. If we can distinguish between aggressive and indolent tumors, there’s a whole group of people who may just need active surveillance.
We need to be able to provide the best cancer care to all people, regardless of race, regardless of gender, regardless of socioeconomics or any other human situation. Achieving health equity is fundamental to who we are as one of the world’s leading cancer centers.