PARP Inhibitors in Prostate Cancer

Praveen Ramakrishnan Geethakumari, Matthew J. Schiewer, Karen E. Knudsen, Wm Kevin Kelly

Research output: Contribution to journalReview articlepeer-review

43 Scopus citations


The genomic landscape of metastatic prostate cancer (mPCa) reveals that up to 90% of patients harbor actionable mutations and >20% have somatic DNA repair gene defects (DRD). This provides the therapeutic rationale of PARP inhibition (PARPi) to achieve “synthetic lethality” in treating this fatal disease. Clinical trials with PARP inhibitors have shown significant response rates up to 88% for PCa patients having DRD like BRCA1/2 or ATM mutations. The FDA has awarded “breakthrough designation” to develop the PARPi olaparib in treating this subset of metastatic PCa patients. The search for predictive biomarkers has expanded the realm of DNA repair genetic defects and combination genetic platforms are being evaluated as tools to assess potential “BRCAness” of tumors. Ongoing clinical trials seek to determine the optimal timing and sequence of using these agents in current PCa treatment algorithms. Combination strategies of PARPi with chemo-, radiation, and hormonal therapies, targeted agents, and immunotherapy are promising avenues of current research. Multi-center international collaborations in well-designed biomarker-driven clinical trials will be key to harness the potential of PARPi in managing a heterogeneous disease like prostate cancer.

Original languageEnglish (US)
Article number37
JournalCurrent treatment options in oncology
Issue number6
StatePublished - Jun 1 2017


  • BRCA
  • BRCAness
  • DNA repair defect (DRD)
  • PARP inhibitor
  • Prostate cancer
  • Synthetic lethality

ASJC Scopus subject areas

  • Oncology
  • Pharmacology (medical)


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