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Review
. 2020 Nov 21;12(11):3467.
doi: 10.3390/cancers12113467.

Therapeutic Potential of PARP Inhibitors in the Treatment of Metastatic Castration-Resistant Prostate Cancer

Albert Jang  1 , Oliver Sartor  1   2 , Pedro C Barata  1   2 , Channing J Paller  3
Affiliations
Review

Therapeutic Potential of PARP Inhibitors in the Treatment of Metastatic Castration-Resistant Prostate Cancer

Albert Jang et al. Cancers (Basel). .

Abstract

Metastatic castration-resistant prostate cancer (mCRPC) is an incurable malignancy with a poor prognosis. Up to 30% of patients with mCRPC have mutations in homologous recombination repair (HRR) genes. Poly (ADP-ribose) polymerase (PARP) inhibitors take advantage of HRR deficiency to kill tumor cells based on the concept of synthetic lethality. Several PARP inhibitors (PARPis) have been successful in various malignancies with HRR gene mutations including BRCA1/2, especially in breast cancer and ovarian cancer. More recently, olaparib and rucaparib were approved for mCRPC refractory to novel hormonal therapies, and other PARPis will likely follow. This article highlights the mechanism of action of PARPis at the cellular level, the preclinical data regarding a proposed mechanism of action and the effectiveness of PARPis in cancer cell lines and animal models. The article expands on the clinical development of PARPis in mCRPC, discusses potential biomarkers that may predict successful tumor control, and summarizes present and future clinical research on PARPis in the metastatic disease landscape.

Keywords: PARP inhibitor; metastatic castration-resistant prostate cancer; niraparib; olaparib; rucaparib; talazoparib.

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Conflict of interest statement

The authors declare no conflict of interest.

References

    1. Saad F., Hotte S.J. Guidelines for the management of castrate-resistant prostate cancer. Can. Urol. Assoc. J. 2010;4:380–384. doi: 10.5489/cuaj.10167. - DOI - PMC - PubMed
    1. Robinson D., Van Allen E.M., Wu Y.M., Schultz N., Lonigro R.J., Mosquera J.M., Montgomery B., Taplin M.E., Pritchard C.C., Attard G., et al. Integrative clinical genomics of advanced prostate cancer. Cell. 2015;161:1215–1228. doi: 10.1016/j.cell.2015.05.001. - DOI - PMC - PubMed
    1. Huang Y., Jiang X., Liang X., Jiang G. Molecular and cellular mechanisms of castration resistant prostate cancer. Oncol. Lett. 2018;15:6063–6076. doi: 10.3892/ol.2018.8123. - DOI - PMC - PubMed
    1. Ryan C.J., Smith M.R., Fizazi K., Saad F., Mulders P.F., Sternberg C.N., Miller K., Logothetis C.J., Shore N.D., Small E.J., et al. Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): Final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 2015;16:152–160. doi: 10.1016/S1470-2045(14)71205-7. - DOI - PubMed
    1. Beer T.M., Armstrong A.J., Rathkopf D., Loriot Y., Sternberg C.N., Higano C.S., Iversen P., Evans C.P., Kim C.S., Kimura G., et al. Enzalutamide in Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer: Extended Analysis of the Phase 3 PREVAIL Study. Eur. Urol. 2017;71:151–154. doi: 10.1016/j.eururo.2016.07.032. - DOI - PMC - PubMed

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