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Annual Review of Medicine

Volume 76, 2025

New Therapeutic Options for BRCA Mutant Patients

  • Anthony Ghanem1 and Susan M. Domchek1,2
  • 1Department of Medicine, University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA; email: [email protected] 2Basser Center for BRCA, Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania, USA
  • Vol. 76:175-187 (Volume publication date January 2025)
  • First published as a Review in Advance on December 04, 2024
  • Copyright © 2025 by the author(s).
    This work is licensed under a Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See credit lines of images or other third-party material in this article for license information.

Abstract

Pathogenic variants in and are associated with significantly elevated lifetime risks of breast, ovarian, pancreatic, and prostate cancer. These genes are critical in double-strand break repair through homologous recombination. An understanding of the biology of and led to the development of targeted therapeutics, specifically poly(ADP-ribose) polymerase (PARP) inhibitors, which are approved by the US Food and Drug Administration for multiple -associated cancers. Here, we discuss the development of PARP inhibitors, mechanisms of resistance, and the potential utility of these drugs beyond canonical tumors, and we describe novel agents under study.

Keyword(s): BRCA1, BRCA2, homologous recombination deficiency, PARP inhibitors, poly(ADP-ribose) polymerase inhibitors
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2025-01-27
2025-06-24
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New Therapeutic Options for BRCA Mutant Patients
Annual Review of Medicine 76, 175 (2025); https://doi.org/10.1146/annurev-med-082523-083843
/content/journals/10.1146/annurev-med-082523-083843
/content/journals/10.1146/annurev-med-082523-083843
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