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2023 PCF Challenge Award

Identifying Drivers of Aggressive Prostate Cancer and Racial Disparities in Patients Presenting with Low-Grade Disease

Principal Investigators: Vanessa Hayes, PhD(The University of Sydney),Gail Prins, PhD (University of Illinois at Chicago), Riana Bornman, MD (University of Pretoria)

Co-Investigators:Massimo Loda, MD (Weill Cornell Medicine), Daniel Moreira, MD (University of Illinois at Chicago), Weerachai Jaratlerdsiri, PhD (The University of Sydney)

Young Investigators: Ikenna Madueke, MD, PhD (University of Illinois at Chicago), Pamela Soh, PhD (The University of Sydney)

Description:

  • African ancestry individuals are at significantly elevated risk for prostate cancer and associated death compared to other ethnic/racial groups. For African ancestry individuals, risk for prostate cancer mortality is further increased with younger age (<65 years) and low-grade disease. What causes this disparity is unknown.
  • Most preclinical and clinical research on prostate cancer biology and treatments has been done in European ancestry populations. The lack of knowledge about prostate cancer biology in African ancestry populations exacerbates prostate cancer racial disparities.
  • This disparity – in which African ancestry patients diagnosed with low-grade disease or at a younger age are at significantly increased risk for lethal disease — raises important concerns with applying current clinical guidelines for managing African ancestry patients. As of now, clinical guidelines exclude divisive action for “low-grade” disease and result in undertreatment and worse outcomes in African ancestry patients.
  • Dr. Vanessa Hayes and team are investigating the etiology of “low-grade” and early onset prostate cancers in African ancestry patients that are ultimately lethal.
  • In this project, the team will define a new classification of African ancestry-relevant “low-grade” and early-onset lethal prostate cancer, to establish a framework and criteria for prostate cancer precision medicine and germline testing for African ancestry patients.
  • The team will perform genomic sequencing on tumors from African ancestry patients from the U.S. and South Africa presenting with low-grade and/or early-onset prostate cancer, to identify cancer driver mutations and inherited genetic cancer risk variants.
  • The impact and relationship of these genomic factors on pathogenicity, oncogenic status and clinical outcomes will be determined.
  • If successful, this project will identify genetic and genomic factors that drive early-onset or “low-grade” prostate cancer that are actually lethal in African ancestry patients. This will enable the development of biomarkers that indicate lethal disease risk in patients diagnosed with “low-grade” disease and clinical guidelines to appropriately manage these patients.

What this means to patients: Identifying the underlying causes of racial prostate cancer health disparities has significant implications for minority inclusion in the benefits of precision medicine, advancing our understanding of the etiology, early detection and ultimately prevention and treatment of lethal prostate cancer. Dr. Hayes and team will identify genetic and genomic risk factors of lethal prostate cancer in African ancestry patients presenting with low-grade or early-onset disease, ultimately translating this into new criteria for classifying, managing and treating prostate cancer in African ancestry patients, and reducing racial health disparities.