The discovery of BRCA1 and BRCA2 as tumor susceptibility genes and their role in genome maintenance has transformed our understanding of hereditary breast and ovarian cancer. This review traces the evolution of BRCA1/2 research over the past 30 years, highlighting key discoveries in the field and their contributions to tumor development. Additionally, we discuss current preventive measures for BRCA1/2 mutation carriers and targeted treatment options based on the concept of synthetic lethality. Finally, we explore the challenges of acquired therapy resistance and discuss potential alternative avenues for targeting BRCA1/2 mutant tumors.

中文翻译：

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BRCA1 和 BRCA2：从癌症易感性到合成致死性


BRCA1 和 BRCA2 作为肿瘤易感基因的发现及其在基因组维持中的作用改变了我们对遗传性乳腺癌和卵巢癌的理解。本综述追溯了过去 30 年 BRCA1/2 研究的演变，重点介绍了该领域的关键发现及其对肿瘤发展的贡献。此外，我们还讨论了当前 BRCA1/2 突变携带者的预防措施和基于合成致死性概念的靶向治疗方案。最后，我们探讨了获得性治疗耐药性的挑战，并讨论了靶向 BRCA1/2 突变肿瘤的潜在替代途径。