{"title":"前列腺癌生殖系变异与治疗意义。","authors":"Masoud Bitaraf, Elena Castro, Nima Sharifi","doi":"10.1016/j.molmed.2025.07.004","DOIUrl":null,"url":null,"abstract":"<p><p>Prostate cancer, the most prevalent noncutaneous cancer and the second leading cause of cancer death among men, is highly heritable. Germline alterations in genes involved in DNA damage repair and the androgen synthesis pathway are associated with worse outcomes. Pathogenic variants in BRCA1, BRCA2, and HSD3B1 are the most prevalent alterations in men with advanced prostate cancer and are associated with increased risk of disease development and progression. These variants are pharmacologically actionable. Poly (ADP-ribose) polymerase (PARP) inhibitors have shown survival benefits in carriers of BRCA1/2 mutations, while HSD3B1 adrenal-permissive carriers might benefit from early intensified androgen blockade treatment. This review explores the impact of pathogenic germline alterations associated with prostate cancer, with a focus on common, clinically actionable variants.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":13.8000,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12321213/pdf/","citationCount":"0","resultStr":"{\"title\":\"Prostate cancer germline variants with therapeutic implications.\",\"authors\":\"Masoud Bitaraf, Elena Castro, Nima Sharifi\",\"doi\":\"10.1016/j.molmed.2025.07.004\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Prostate cancer, the most prevalent noncutaneous cancer and the second leading cause of cancer death among men, is highly heritable. Germline alterations in genes involved in DNA damage repair and the androgen synthesis pathway are associated with worse outcomes. Pathogenic variants in BRCA1, BRCA2, and HSD3B1 are the most prevalent alterations in men with advanced prostate cancer and are associated with increased risk of disease development and progression. These variants are pharmacologically actionable. Poly (ADP-ribose) polymerase (PARP) inhibitors have shown survival benefits in carriers of BRCA1/2 mutations, while HSD3B1 adrenal-permissive carriers might benefit from early intensified androgen blockade treatment. This review explores the impact of pathogenic germline alterations associated with prostate cancer, with a focus on common, clinically actionable variants.</p>\",\"PeriodicalId\":23263,\"journal\":{\"name\":\"Trends in molecular medicine\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":13.8000,\"publicationDate\":\"2025-07-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12321213/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Trends in molecular medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.molmed.2025.07.004\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Trends in molecular medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.molmed.2025.07.004","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Prostate cancer germline variants with therapeutic implications.
Prostate cancer, the most prevalent noncutaneous cancer and the second leading cause of cancer death among men, is highly heritable. Germline alterations in genes involved in DNA damage repair and the androgen synthesis pathway are associated with worse outcomes. Pathogenic variants in BRCA1, BRCA2, and HSD3B1 are the most prevalent alterations in men with advanced prostate cancer and are associated with increased risk of disease development and progression. These variants are pharmacologically actionable. Poly (ADP-ribose) polymerase (PARP) inhibitors have shown survival benefits in carriers of BRCA1/2 mutations, while HSD3B1 adrenal-permissive carriers might benefit from early intensified androgen blockade treatment. This review explores the impact of pathogenic germline alterations associated with prostate cancer, with a focus on common, clinically actionable variants.
期刊介绍：
Trends in Molecular Medicine (TMM) aims to offer concise and contextualized perspectives on the latest research advancing biomedical science toward better diagnosis, treatment, and prevention of human diseases. It focuses on research at the intersection of basic biology and clinical research, covering new concepts in human biology and pathology with clear implications for diagnostics and therapy. TMM reviews bridge the gap between bench and bedside, discussing research from preclinical studies to patient-enrolled trials. The major themes include disease mechanisms, tools and technologies, diagnostics, and therapeutics, with a preference for articles relevant to multiple themes. TMM serves as a platform for discussion, pushing traditional boundaries and fostering collaboration between scientists and clinicians. The journal seeks to publish provocative and authoritative articles that are also accessible to a broad audience, inspiring new directions in molecular medicine to enhance human health.
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