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Response prediction biomarkers and drug combinations of PARP inhibitors in prostate cancer

Abstract

PARP inhibitors are a group of inhibitors targeting poly(ADP-ribose) polymerases (PARP1 or PARP2) involved in DNA repair and transcriptional regulation, which may induce synthetic lethality in BRCAness tumors. Systematic analyzes of genomic sequencing in prostate cancer show that ~10%–19% of patients with primary prostate cancer have inactivated DNA repair genes, with a notably higher proportion of 23%–27% in patients with metastatic castration-resistant prostate cancer (mCRPC). These characteristic genomic alterations confer possible vulnerability to PARP inhibitors in patients with mCRPC who benefit only modestly from other therapies. However, only a small proportion of patients with mCRPC shows sensitivity to PARP inhibitors, and these sensitive patients cannot be fully identified by existing response prediction biomarkers. In this review, we provide an overview of the potential response prediction biomarkers and synergistic combinations studied in the preclinical and clinical stages, which may expand the population of patients with prostate cancer who may benefit from PARP inhibitors.

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Fig. 1: The antitumor effect of PARP inhibitors.

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Acknowledgements

This work was supported by the National Key Research and Development Program of China (2016YFC1306900), National Natural Science Foundation of China (81874327), Key Research and Development Program of Hunan Province (2019SK2251), and Innovation and Research Project of Development and Reform Committee of Hunan Province (2019-875).

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Correspondence to Zhao-qian Liu.

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Chen, Yx., Tan, Lm., Gong, Jp. et al. Response prediction biomarkers and drug combinations of PARP inhibitors in prostate cancer. Acta Pharmacol Sin (2021). https://doi.org/10.1038/s41401-020-00604-1

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Keywords

  • prostate cancer
  • PARP inhibitors
  • response prediction biomarkers
  • synergistic combination strategies

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