PARP inhibitors for homologous recombination-deficient prostate cancer

Eric S. Christenson, Emmanuel S. Antonarakis

Research output: Contribution to journalReview articlepeer-review

14 Scopus citations

Abstract

Introduction: Prostate adenocarcinoma represents a leading cause of cancer-related mortality. Increased emphasis on understanding the molecular basis of prostate cancer has identified a substantial burden of homologous recombination (HR) pathway mutations, which are enriched in castrate-resistant disease. This discovery has yielded novel therapeutic opportunities. Areas covered: We will discuss the treatment of castrate-resistant prostate cancer (CRPC), with a focus on the use of poly (ADP-ribose) polymerase (PARP) inhibitors in this space. Evidence for use in HR-deficient patients will be outlined with discussion of the mechanism of action for this drug class, pathways of resistance, and approaches for expanding PARP inhibitor use to non–HR-deficient prostate cancer subgroups. Expert opinion: PARP inhibition represents an exciting tool for management of HR-inactivated CRPC. With rapid adoption of next-generation sequencing technologies and other molecular techniques, the number of patients in this category is likely to increase. Ongoing and future investigations will be critical for improved understanding of the promise and appropriate treatment sequencing of PARP inhibition and optimal options for HR-proficient and -deficient prostate cancer populations. Questions remain about the clinical significance of monoallelic vs. biallelic HR mutations, the relevance of germline vs. somatic-only mutations, and the importance of mutations in non-canonical HR genes.

Original languageEnglish (US)
Pages (from-to)123-133
Number of pages11
JournalExpert Opinion on Emerging Drugs
Volume23
Issue number2
DOIs
StatePublished - Apr 3 2018
Externally publishedYes

Bibliographical note

Funding Information:
This work was partially supported by National Institutes of Health Grant P30 CA006973 (E.S.A.), the Patrick C. Walsh fund (E.S.A) and the Prostate Cancer Foundation (E.S.A). The content is solely the responsibility of the authors and does not represent the official views of the National Cancer Institute or the National Institutes of Health.

Publisher Copyright:
© 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group.

Keywords

  • DNA repair
  • PARP inhibitors
  • castrate resistant prostate carcinoma
  • homologous recombination deficiency
  • niraparib
  • olaparib
  • rucaparib

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