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2020 CRIS Cancer Foundation-Thomas H. Lee-PCF Young Investigator Award

Improving Outcomes for PARP Inhibition Treatment in Men with Lethal BRCA2 Mutant Prostate Cancer by Targeting the Tumor Microenvironment

Anastasia Hepburn, PhD

Newcastle University

Mentors: Rakesh Heer, PhD; Robert Bristow, MD

Description:

  • PARP-inhibitors are new precision medicines that have recently received FDA-approval for the treatment of advanced prostate cancer with certain DNA damage repair (DDR) gene alterations.
  • BRCA2is the most commonly mutated DDR gene in prostate cancer. BRCA2-mutated prostate cancer are particularly aggressive, but are also highly responsive to PARP inhibitors. Unfortunately, ~ 20% of patients with BRCA2 alterations do not respond to treatment with PARP inhibitors. Alternative therapeutic strategies are urgently needed for these patients.
  • Dr. Anastasia Hepburn is studying the biology of treatment resistance to PARP-inhibitors in patients withBRCA2alterations.
  • In this project, Dr. Hepburn will develop newBRCA2-mutated prostate cancer models to study the biology by which low tumor oxygen levels (hypoxia) contribute to PARP inhibitor sensitivity.
  • Candidate targets for new therapies to be used in combination with PARP inhibitors inBRCA2-mutated prostate cancer will be identified and tested in these models.
  • If successful, this project could identify new therapeutic approaches for testing in clinical trials, potentially informing new prostate cancer precision medicine strategies for this subclass of patients.

What this means to patients: Dr. Hepburn is studying mechanisms of PARP inhibitor resistance inBRCA2-mutated prostate cancer and identifying new combination treatment strategies that will lead to improved outcomes for these patients.