Treatment of metastatic castration-resistant prostate cancer: Are PARP inhibitors shifting the paradigm?

Naohiro Fujimoto, Kenichi Harada, Masaki Shiota, Ikko Tomisaki, Akinori Minato, Yujiro Nagata, Rieko Kimuro, Mirii Harada, Masato Fujisawa

Research output: Contribution to journalReview articlepeer-review

Abstract

Remarkable developments in the treatment of metastatic castration-resistant prostate cancer (mCRPC) have been achieved over the past decade. Although targeting the novel androgen receptor axis and using chemotherapeutic agents have improved survival, mCRPC is still a lethal disease. A better molecular characterization of cancer resulted in the determination of the important role of homologous recombination repair (HRR) genes in cancer development, and poly (ADP-ribose) polymerase (PARP) is one of the most attractive therapeutic targets. Recent clinical studies have demonstrated that PARP inhibitors significantly improve oncological outcomes in patients with mCRPC harboring BRCA mutations, and PARP inhibitors are becoming a standard of care for these patients. However, not only PARP inhibitors, but also chemotherapeutic agents such as platinum agents, taxanes, and radium-223 are active in HRR gene mutation carriers, and platinum sensitivity may predict the efficacy of PARP inhibitors for mCRPC. The combination of PARP inhibitors with other anti-cancer agents may overcome resistance mechanisms against PARP inhibitors and lead to survival benefits. Appropriate treatment sequences and combinations may change the therapeutic landscape of DNA repair deficient mCRPC.

Original languageEnglish
Pages (from-to)4687-4695
Number of pages9
JournalAnticancer research
Volume41
Issue number10
DOIs
Publication statusPublished - Oct 2021

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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