Targeting the BRCA1/2 Deficient Cancer With Parp Inhibitors: Clinical Outcomes and Mechanistic Insights
Title
Targeting the BRCA1/2 Deficient Cancer With Parp Inhibitors: Clinical Outcomes and Mechanistic Insights
Date
2023
Publisher
Frontiers Medicine SA
Subject
BRCA1 and BRCA2
Biology (General)
PARP inhibitors
PARP1
Breast cancer
Ovarian cancer
Synthetic lethality
Biology (General)
PARP inhibitors
PARP1
Breast cancer
Ovarian cancer
Synthetic lethality
Language
English
Abstract
BRCA1 and BRCA2 play a critical role in a variety of molecular processes related to DNA metabolism, including homologous recombination and mediating the replication stress response. Individuals with mutations in the BRCA1 and BRCA2 (BRCA1/2) genes have a significantly higher risk of developing various types of cancers, especially cancers of the breast, ovary, pancreas, and prostate. Currently, the Food and Drug Administration (FDA) has approved four PARP inhibitors (PARPi) to treat cancers with BRCA1/2 mutations. In this review, we will first summarize the clinical outcomes of the four FDA-approved PARPi in treating BRCA1/2 deficient cancers. We will then discuss evidence supporting the hypothesis that the cytotoxic effect of PARPi is likely due to inducing excessive replication stress at the difficult-to-replicate (DTR) genomic regions in BRCA1/2 mutated tumors. Finally, we will discuss the ongoing preclinical and clinical studies on how to combine the PARPi with immuno-oncology drugs to further improve clinical outcomes.
Source
Frontiers in Cell and Developmental Biology, Volume 11, March 2023, pages 1133472–1133472
Rights
Copyright © 2023 Ragupathi, Singh, Perez and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Format
PDF
Type
Text
Identifier
Bibliographic Citation
Ragupathi, A., Singh, M., Perez, A. M., & Zhang, D. (2023). Targeting the BRCA1/2 deficient cancer with PARP inhibitors: Clinical outcomes and mechanistic insights. In Frontiers in Cell and Developmental Biology (Vol. 11). Frontiers Media SA. https://doi.org/10.3389/fcell.2023.1133472
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Collection
Citation
Ragupathi, A., Singh, M., Perez, A. M., & Zhang, D., Targeting the BRCA1/2 Deficient Cancer With Parp Inhibitors: Clinical Outcomes and Mechanistic Insights. Frontiers in Cell and Developmental Biology, Volume 11, March 2023, pages 1133472–1133472, New York Tech Institutional Repository, accessed April 27, 2024, https://repository.nyitlibrary.org/items/show/3778
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