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Clinical Development of PARP Inhibitors in Treating Metastatic Castration-Resistant Prostate Cancer

1
Department of Internal Medicine, University of South Florida, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA
2
Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center & Research Institute, 12902 USF Magnolia Drive, Tampa, FL 33612, USA
*
Author to whom correspondence should be addressed.
Cells 2019, 8(8), 860; https://doi.org/10.3390/cells8080860
Received: 17 July 2019 / Revised: 4 August 2019 / Accepted: 7 August 2019 / Published: 9 August 2019
(This article belongs to the Special Issue Molecular Role of PARP in Health and Disease)
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PDF [1011 KB, uploaded 9 August 2019]

Abstract

The approval of upfront abiraterone for castration-sensitive prostate cancer and the approval of enzalutamide and apalutamide for non-metastatic castration-resistant prostate cancer have led to early utilization of potent androgen receptor (AR) signaling inhibitors in treating advanced prostate cancer. There is an unmet need to develop novel therapies beyond targeting AR signaling for metastatic castration-resistant prostate cancer (mCRPC). Poly (ADP-ribose) polymerase inhibitors (PARPi) belong to a class of targeted agents being developed for the treatment of homologous recombination repair (HRR) deficient tumors. Olaparib, rucaparib, niraparib, veliparib, and talazoparib were evaluated in early phase trials as a monotherapy for HRR-deficient mCRPC. Among them, olaparib and rucaparib have breakthrough designations for BRCA1/2-mutated mCRPC. Phase II studies also reported clinical activity of the PARPi and abiraterone combination and the PARPi checkpoint inhibitor combination in HRR-intact mCRPC. Ongoing phase III trials are testing these combinations as frontline or later line treatments for mCRPC. This review summarizes the critical clinical data as well as ongoing clinical trials for developing PARPi in treating mCRPC. View Full-Text
Keywords: PARP inhibitors; DNA damage repair deficiency; prostate cancer; targeted therapy PARP inhibitors; DNA damage repair deficiency; prostate cancer; targeted therapy
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Adashek, J.J.; Jain, R.K.; Zhang, J. Clinical Development of PARP Inhibitors in Treating Metastatic Castration-Resistant Prostate Cancer. Cells 2019, 8, 860.

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