Researchers to utilize $7.6M and the latest technology to better understand prostate cancer predictors

Researchers with the RESPOND (Research on Prostate Cancer in Men of African Ancestry: Defining the Roles of Genetics, Tumor Markers, and Social Stress) study have been awarded $7.6M from the National Cancer Institute of the National Institutes of Health to continue following prostate cancer patients of African descent over the next five years. A multilevel study that was initially funded in 2018, RESPOND is the first of its kind to have established a large cohort of patients across the country.

African American men have an 70% greater chance of being diagnosed with prostate cancer than white men, and despite being more than twice as likely to die from the disease, the causes of these disparities are not yet known. Christopher Haiman, ScD, professor of population and public health sciences and director of the Center for Genetic Epidemiology at Keck School of Medicine of USC, and his team of researchers will spend the next several years leveraging cohort data to better understand cancer predictors among this population.

“It’s unique in that a lot of these questions have been asked in the past in smaller samples, and each study focusing on a different dimension – lifestyle, genetics, social factors, tumor genetics or tumor molecular characteristics – and this is a study where we’re integrating all of this information together,” explains Haiman. “It really helps us understand the underlying factors and how they relate to one another and contribute to the higher mortality in this population.”

Under the guidance of Ann Hamilton, PhD, research professor of population and public health sciences, the team previously recruited over 12,500 African American men diagnosed with prostate cancer from seven states in different geographic areas of the country. There are a number of key areas the team aims to concentrate on as they follow patients – access to care; structural and social stressors, with a concentration on persistently disinvested neighborhoods; lifestyle, comorbidities, genetic risk, tumor molecular features; and machine-driven deep learning applied to pathologic imaging to improve prediction of disease trajectory.

Haiman and his team are taking advantage of the latest technologies available, which he notes have advanced even since they began a few years ago.

“When we put the grant in, we were going to do whole-exome sequencing. Now the technology is better and the costs of whole-genome sequencing has gone down, so about 7,500 of them [who submitted DNA samples] are going to be getting whole-genome sequencing, which is taking place right now,” explains Haiman, who credits David Conti, PhD, professor of population and public health sciences, with leading the data science and management components of the study.

The team is also taking advantage of artificial intelligence, working with Tamara Lotan at Johns Hopkins University and Aira Matrix to analyze images of tumors.

“We scan tumor samples and based on the pathologic features one can extract information out using AI,” says Haiman. “Our goal is to try and identify if there are features on the slide which are more informative than the clinical indicators normally used like a Gleason Score, that are going to help us determine prognosis and survival.” It is something he says was not possible five years ago when the study began and has potentially huge implications for pathology.

“Pathology’s hard, and there’s such variability in pathologists and expertise,” says Haiman. “If you can just scan an image and apply an algorithm to it, you can get the information back, wherever you are, globally. I think it has a huge effect on leveling the play field for providing important precision-based medicine information back to patients in low resource settings.”

In addition to RESPOND, Haiman is a recipient of the ACS Impact Professorship Award, focused on understanding the higher burden of prostate cancer among African American men. He is also the recipient of an award from the Prostate Cancer Foundation and Robert F. Smith towards developing a more reliable genetic risk prediction model for prostate cancer for African American men.

Additional researchers and team leaders include Iona Cheng, PhD, MPH, Scarlett Gomez, MPH, PhD and Tamara Lotan, MD. RESPOND is funded by the National Cancer Institute of the National Institutes of Health under award number U01CA287036.