Personalized medicine for metastatic prostate cancer: The paradigm of PARP inhibitors

Crit Rev Oncol Hematol. 2023 Dec:192:104157. doi: 10.1016/j.critrevonc.2023.104157. Epub 2023 Oct 18.

Abstract

Despite remarkable progress in the last decade, metastatic prostate cancer (mPCa) remains incurable. The approval of PARP inhibitors (PARPis) represents a milestone in this field, which definitively enters the era of precision medicine, as mPCa is often enriched for defects of homologous recombination repair genes. PARPis are now used as single agents for patients with metastatic castration-resistant PCa. Moreover, combinations of PARPis plus androgen-receptor targeted agents and immune checkpoint inhibitors, and earlier applications of PARPis in the metastatic hormone-sensitive PCa are under evaluation, representing the possible upcoming applications of these agents. Mechanisms of sensitization and resistance have been only partially elucidated. In our review, we summarize the current clinical evidence regarding PARPis in mPCa and the future directions of these targeted agents.

Keywords: BRCA; Biomarker; Olaparib; PARP inhibitor; Prostate cancer; Rucaparib.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents* / therapeutic use
  • Humans
  • Poly(ADP-ribose) Polymerase Inhibitors / pharmacology
  • Poly(ADP-ribose) Polymerase Inhibitors / therapeutic use
  • Precision Medicine
  • Prostatic Neoplasms* / drug therapy
  • Prostatic Neoplasms* / genetics
  • Prostatic Neoplasms* / pathology

Substances

  • Antineoplastic Agents
  • Poly(ADP-ribose) Polymerase Inhibitors