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The Role of PARP Inhibitors in the Treatment of Prostate Cancer: Recent Advances in Clinical Trials
Poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPis) belong to a class of targeted drugs developed for the treatment of homologous recombination repair (HRR)-defective tumors. Preclinical and limited clinical data suggest that PARP inhibition is effective against prostate cancer (PC) i...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150298/ https://www.ncbi.nlm.nih.gov/pubmed/34066020 http://dx.doi.org/10.3390/biom11050722 |
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author | Xia, Mingyue Guo, Zhigang Hu, Zhigang |
author_facet | Xia, Mingyue Guo, Zhigang Hu, Zhigang |
author_sort | Xia, Mingyue |
collection | PubMed |
description | Poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPis) belong to a class of targeted drugs developed for the treatment of homologous recombination repair (HRR)-defective tumors. Preclinical and limited clinical data suggest that PARP inhibition is effective against prostate cancer (PC) in patients with HRR-deficient tumors and that PARPis can improve the mortality rate of PC in patients with BRCA1/2 mutations through a synthetic lethality. Olaparib has been approved by the FDA for advanced ovarian and breast cancer with BRCA mutations, and as a maintenance therapy for ovarian cancer after platinum chemotherapy. PARPis are also a new and emerging clinical treatment for metastatic castration-resistant prostate cancer (mCRPC). Although PARPis have shown great efficacy, their widespread use is restricted by various factors, including drug resistance and the limited population who benefit from treatment. It is necessary to study the combination of PARPis and other therapeutic agents such as anti-hormone drugs, USP7 inhibitors, BET inhibitors, and immunotherapy. This article reviews the mechanism of PARP inhibition in the treatment of PC, the progress of clinical research, the mechanisms of drug resistance, and the strategies of combination treatments. |
format | Online Article Text |
id | pubmed-8150298 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-81502982021-05-27 The Role of PARP Inhibitors in the Treatment of Prostate Cancer: Recent Advances in Clinical Trials Xia, Mingyue Guo, Zhigang Hu, Zhigang Biomolecules Review Poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPis) belong to a class of targeted drugs developed for the treatment of homologous recombination repair (HRR)-defective tumors. Preclinical and limited clinical data suggest that PARP inhibition is effective against prostate cancer (PC) in patients with HRR-deficient tumors and that PARPis can improve the mortality rate of PC in patients with BRCA1/2 mutations through a synthetic lethality. Olaparib has been approved by the FDA for advanced ovarian and breast cancer with BRCA mutations, and as a maintenance therapy for ovarian cancer after platinum chemotherapy. PARPis are also a new and emerging clinical treatment for metastatic castration-resistant prostate cancer (mCRPC). Although PARPis have shown great efficacy, their widespread use is restricted by various factors, including drug resistance and the limited population who benefit from treatment. It is necessary to study the combination of PARPis and other therapeutic agents such as anti-hormone drugs, USP7 inhibitors, BET inhibitors, and immunotherapy. This article reviews the mechanism of PARP inhibition in the treatment of PC, the progress of clinical research, the mechanisms of drug resistance, and the strategies of combination treatments. MDPI 2021-05-12 /pmc/articles/PMC8150298/ /pubmed/34066020 http://dx.doi.org/10.3390/biom11050722 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Xia, Mingyue Guo, Zhigang Hu, Zhigang The Role of PARP Inhibitors in the Treatment of Prostate Cancer: Recent Advances in Clinical Trials |
title | The Role of PARP Inhibitors in the Treatment of Prostate Cancer: Recent Advances in Clinical Trials |
title_full | The Role of PARP Inhibitors in the Treatment of Prostate Cancer: Recent Advances in Clinical Trials |
title_fullStr | The Role of PARP Inhibitors in the Treatment of Prostate Cancer: Recent Advances in Clinical Trials |
title_full_unstemmed | The Role of PARP Inhibitors in the Treatment of Prostate Cancer: Recent Advances in Clinical Trials |
title_short | The Role of PARP Inhibitors in the Treatment of Prostate Cancer: Recent Advances in Clinical Trials |
title_sort | role of parp inhibitors in the treatment of prostate cancer: recent advances in clinical trials |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150298/ https://www.ncbi.nlm.nih.gov/pubmed/34066020 http://dx.doi.org/10.3390/biom11050722 |
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