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Updated: Aug 24, 2025

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
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The evolving landscape of PARP inhibitors in castration-resistant prostate cancer: a spotlight on treatment

Benjamin A Teply1, Emmanuel S Antonarakis2

  • 1Division of Hematology/Oncology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA.

Expert Review of Clinical Pharmacology
|October 26, 2022
PubMed
Abstract

Insights

PARP inhibitors are standard care for metastatic castration-resistant prostate cancer (mCRPC) with HRR deficiency. Combination therapies may expand benefits for more patients, especially those without BRCA mutations.

Area of Science:

  • Oncology
  • Genitourinary Cancers
  • Genetics

Background:

  • PARP inhibition is a standard treatment for metastatic castration-resistant prostate cancer (mCRPC) in patients with homologous recombination repair deficiency (HRRd).
  • Treatment efficacy and patient selection depend on the specific PARP inhibitor and the nature of the HRR defect.
  • Identifying optimal patient populations and combination strategies is crucial for expanding treatment benefits.

Approach:

  • This review examines the clinical development of FDA-approved PARP inhibitors (olaparib, rucaparib) in prostate cancer.
  • It assesses the status of experimental PARP inhibitors using published literature and clinical trial data.
  • The review focuses on emerging combination therapies, particularly with novel androgen receptor signaling inhibitors.

Key Points:

  • Olaparib demonstrates clear benefit for mCRPC patients with BRCA1/2 mutations.
  • The benefit of PARP inhibitors for other HRR mutations is less defined, with alternative treatments available.
  • Combination therapies are essential for extending PARP inhibitor benefits to patients lacking BRCA1/2 mutations.

Conclusions:

  • PARP inhibitors represent a significant advancement in mCRPC treatment for HRRd patients.
  • Further research into combination strategies is vital to broaden the application of PARP inhibition.
  • Personalized medicine approaches, considering specific genetic defects, will optimize treatment outcomes.
Keywords:
PARP inhibitionProstate cancerhomologous recombination repair deficiencyhormone therapy

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