Tutt A N J, Lord C J, McCabe N, Farmer H, Turner N, Martin N M, Jackson S P, Smith G C M, Ashworth A
The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London, UK.
Cold Spring Harb Symp Quant Biol. 2005;70:139-48. doi: 10.1101/sqb.2005.70.012.
Individuals harboring germ-line mutations in the BRCA1 or BRCA2 genes are at highly elevated risk of a variety of cancers. Ten years of research has revealed roles for BRCA1 and BRCA2 in a wide variety of cellular processes. However, it seems likely that the function of these proteins in DNA repair is critically important in maintaining genome stability. Despite this increasing knowledge of the defects present in BRCA-deficient cells, BRCA mutation carriers developing cancer are still treated similarly to sporadic cases. Here we describe our efforts, based on understanding the DNA repair defects in BRCAdeficient cells, to define the optimal existing treatment for cancers arising in BRCA mutation carriers and, additionally, the development of novel therapeutic approaches. Finally, we discuss how therapies developed to treat BRCA mutant tumors might be applied to some sporadic cancers sharing similar specific defects in DNA repair.
携带BRCA1或BRCA2基因种系突变的个体患多种癌症的风险极高。十年的研究揭示了BRCA1和BRCA2在多种细胞过程中的作用。然而，这些蛋白质在DNA修复中的功能对于维持基因组稳定性似乎至关重要。尽管对BRCA缺陷细胞中存在的缺陷的了解越来越多，但患癌的BRCA突变携带者仍与散发性病例接受类似的治疗。在此，我们基于对BRCA缺陷细胞中DNA修复缺陷的理解，描述了我们为确定BRCA突变携带者所患癌症的最佳现有治疗方法以及开发新治疗方法所做的努力。最后，我们讨论了针对BRCA突变肿瘤开发的疗法如何应用于一些在DNA修复中存在类似特定缺陷的散发性癌症。
