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2020 Gary and Allison Lieberman-PCF VAlor Young Investigator Award

Towards Targeting African American Prostate Cancer with PARP Inhibitors and Immunotherapy

Kara Maxwell, MD, PhD

Corporal Michael J. Crescenz VA Medical Center; University of Pennsylvania

Mentors: Naomi Haas, MD; Kyle Robinson, MD

Description:

  • African American men have a significantly higher chance of developing prostate cancer and dying from prostate cancer compared to men of European descent. The cause of this disparity is likely multi-factorial and may be due to biological, environmental or social factors, or a complex interaction of all three.
  • Dr. Kara Maxwell is investigating the genetic mechanisms underlying the efficacy of PARP inhibitors and checkpoint immunotherapy treatments for African American prostate cancer. These treatments are approved for the treatment of prostate cancer patients who have certain tumor alterations.
  • In this project, Dr. Maxwell will study the genomic and gene expression biology of prostate tumors from African American vs. European American Veterans to identify the genetic mechanisms underlying homologous recombination DNA repair deficiency. This type of DNA repair alterations may render tumors sensitive to treatment with PARP inhibitors.
  • In addition, Dr. Maxwell will study the genomic and gene expression of tumors to identify the genetic mechanisms underlying mismatch DNA repair deficiency in African American vs European American prostate tumors. This type of DNA repair alterations may render tumors sensitive to checkpoint immunotherapy.
  • Finally, Dr. Maxwell will establish organoid models of homologous recombination and mismatch DNA repair deficient prostate cancer from African American patients to directly study PARP inhibitor and check point immunotherapy responses.
  • If successful, this project will provide data on the mechanisms of DNA repair deficient phenotypes in African American prostate cancer, including from a veteran population. The study will identify the appropriate genetic biomarkers to understand DNA repair based drug response and resistance.

What this means to patients: Dr. Maxwell will provide a comprehensive analysis of the genomic and other molecular alterations that render prostate tumors sensitive to treatment with the recently FDA-approved prostate cancer precision medicines, PARP inhibitors and checkpoint immunotherapy, in the African American Veteran population. These studies will inform new clinical trials and the way African American patients, including the vulnerable Veteran population, with aggressive and lethal prostate cancer are treated clinically.