{"title":"New Therapeutic Options for BRCA Mutant Patients.","authors":"Anthony Ghanem, Susan M Domchek","doi":"10.1146/annurev-med-082523-083843","DOIUrl":null,"url":null,"abstract":"<p><p>Pathogenic variants in <i>BRCA1</i> and <i>BRCA2</i> 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 <i>BRCA1</i> and <i>BRCA2</i> 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 <i>BRCA1/2</i>-associated cancers. Here, we discuss the development of PARP inhibitors, mechanisms of resistance, and the potential utility of these drugs beyond canonical <i>BRCA1/2</i> tumors, and we describe novel agents under study.</p>","PeriodicalId":8056,"journal":{"name":"Annual review of medicine","volume":" ","pages":""},"PeriodicalIF":15.1000,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annual review of medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1146/annurev-med-082523-083843","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
Abstract
Pathogenic variants in BRCA1 and BRCA2 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 BRCA1 and BRCA2 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 BRCA1/2-associated cancers. Here, we discuss the development of PARP inhibitors, mechanisms of resistance, and the potential utility of these drugs beyond canonical BRCA1/2 tumors, and we describe novel agents under study.
期刊介绍：
The Annual Review of Medicine, which has been published since 1950, focuses on important advancements in diverse areas of medicine. These include AIDS/HIV, cardiology, clinical pharmacology, dermatology, endocrinology/metabolism, gastroenterology, genetics, immunology, infectious disease, neurology, oncology/hematology, pediatrics, psychiatry, pulmonology, reproductive medicine, and surgery. The journal's current volume has transitioned from a gated access model to an open access model through the Annual Reviews' Subscribe to Open program. All articles published in the journal are now available under a CC BY license.
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