The evolving landscape of PARP inhibitors in castration-resistant prostate cancer: a spotlight on treatment combinations

Benjamin A. Teply, Emmanuel S. Antonarakis

Research output: Contribution to journalReview articlepeer-review


Introduction: PARP inhibition in prostate cancer has become a standard-of-care option for men with metastatic castration-resistant prostate cancer (mCRPC) with deficiency in homologous recombination repair (HRRd). The benefit varies based upon the characteristics of the PARP inhibitor used and the underlying HRR defect. Optimal patient selection remains a clinical challenge, and investigations are underway to identify effective combination therapies to expand the population that benefits. Areas covered: We review the clinical development of the FDA-approved PARP inhibitors olaparib and rucaparib. Additionally, we explore the status of other PARP inhibitors that remain experimental in prostate cancer, based upon review of published abstracts, articles, and Most new studies, including phase 3 trials for talazoparib and rucaparib, involve combinations with novel androgen receptor signaling inhibitors. We review the landscape of emerging PARP inhibitor-based combination therapies. Expert opinion: For men with BRCA1 or BRCA2 mutations, olaparib has a clear role for early use in the disease course of mCRPC. For men with other HRR mutations, that benefit remains less well defined, particularly with the availability of other treatment choices. Ultimately, combination strategies are likely to be the best avenue for men without BRCA1 or BRCA2 mutations to be treated with PARP inhibition.

Original languageEnglish (US)
Pages (from-to)1293-1304
Number of pages12
JournalExpert Review of Clinical Pharmacology
Issue number11
StatePublished - 2022

Bibliographical note

Funding Information:
This paper was not funded.

Publisher Copyright:
© 2022 Informa UK Limited, trading as Taylor & Francis Group.


  • PARP inhibition
  • Prostate cancer
  • homologous recombination repair deficiency
  • hormone therapy

PubMed: MeSH publication types

  • Review
  • Journal Article


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