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2025 Michael and Lori Milken Family Foundation – PCF Challenge Award

PARP Inhibition with SABR for High-Risk Mutation Oligometastatic Castration-Sensitive Prostate Cancer

Principal Investigators: Matthew Deek, MD (Rutgers Biomedical and Health Sciences), Phuoc Tran, MD, PhD (The University of Texas MD Anderson Cancer Center), Shuang Zhao, MD, MSc (University of Wisconsin), Ke Nie, MD (Rutgers Biomedical and Health Sciences)

Description:

  • Once prostate cancer has metastasized, it has generally been considered incurable, although several life-prolonging treatments are now available. Oligometastatic prostate cancer is a state of metastatic disease where there are fewer than ~5 metastatic sites, and researchers are investigating whether different treatment strategies should be used in these patients.
  • Several recent clinical trials in patients with oligometastatic prostate cancer have demonstrated treating metastases with high precision radiation called stereotactic ablative radiation (SABR) can delay cancer progression. While these trials are promising, not all patients benefited equally from this therapy.
  • Dr. Deek and team have found that certain genomic alterations in tumor cells might predict for response to radiation, and high-risk mutations in specific genes are associated with poorer response to therapy and thus these patients need novel treatment strategies. The team has initiated a clinical trial in patients with oligometastatic prostate cancer and high-risk mutations to investigate how to better personalize therapy by testing SABR plus androgen deprivation therapy (ADT) only vs. with the addition of targeted therapies (AR-targeted therapy and PARP-inhibitors). 
  • In this project, the team will perform translational science studies to understand patients’ response to radiation and targeted therapy on the clinical trial. Specifically, the team will determine whether tumor genomic alterations from circulating tumor cells and circulating tumor DNA, imaging features on PET scans taken before treatment, and/or artificial intelligence-based features from pathology slides, can help predict response to these different treatment combinations on the clinical trial.
  • If successful, this project will develop biomarkers to predict which patients with oligometastatic prostate cancer will benefit from radiation and targeted therapies, and result in a new personalized therapy strategy for patients.

What this means to patients: Oligometastatic prostate cancer is an early state of metastatic prostate cancer, and some patients have benefitted from high precision radiation to these metastatic sites. Dr. Deek and team are conducting a clinical trial to investigate the efficacy of radiation combined with systemic therapies in patients with oligometastatic prostate cancer to assess if whether patients with certain high-risk mutations benefit from the addition targeted therapies. This project will define biomarkers for response to these treatment options and will result in a new precision medicine strategy for patients with advanced prostate cancer.