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

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 canc...

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Detalles Bibliográficos
Autores principales: Adashek, Jacob J., Jain, Rohit K., Zhang, Jingsong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721701/
https://www.ncbi.nlm.nih.gov/pubmed/31404966
http://dx.doi.org/10.3390/cells8080860
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author Adashek, Jacob J.
Jain, Rohit K.
Zhang, Jingsong
author_facet Adashek, Jacob J.
Jain, Rohit K.
Zhang, Jingsong
author_sort Adashek, Jacob J.
collection PubMed
description 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.
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spelling pubmed-67217012019-09-10 Clinical Development of PARP Inhibitors in Treating Metastatic Castration-Resistant Prostate Cancer Adashek, Jacob J. Jain, Rohit K. Zhang, Jingsong Cells Review 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. MDPI 2019-08-09 /pmc/articles/PMC6721701/ /pubmed/31404966 http://dx.doi.org/10.3390/cells8080860 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Adashek, Jacob J.
Jain, Rohit K.
Zhang, Jingsong
Clinical Development of PARP Inhibitors in Treating Metastatic Castration-Resistant Prostate Cancer
title Clinical Development of PARP Inhibitors in Treating Metastatic Castration-Resistant Prostate Cancer
title_full Clinical Development of PARP Inhibitors in Treating Metastatic Castration-Resistant Prostate Cancer
title_fullStr Clinical Development of PARP Inhibitors in Treating Metastatic Castration-Resistant Prostate Cancer
title_full_unstemmed Clinical Development of PARP Inhibitors in Treating Metastatic Castration-Resistant Prostate Cancer
title_short Clinical Development of PARP Inhibitors in Treating Metastatic Castration-Resistant Prostate Cancer
title_sort clinical development of parp inhibitors in treating metastatic castration-resistant prostate cancer
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721701/
https://www.ncbi.nlm.nih.gov/pubmed/31404966
http://dx.doi.org/10.3390/cells8080860
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