Ashworth Alan
The Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Fulham Road, London, United Kingdom.
Cancer Res. 2008 Dec 15;68(24):10021-3. doi: 10.1158/0008-5472.CAN-08-2287.
Cells carrying mutated BRCA1 or BRCA2 genes are defective in DNA repair by homologous recombination and, as a consequence, are highly sensitive to inhibitors of poly (ADP-ribose) polymerase (PARP). This provides the basis for a novel "synthetic lethal" approach to cancer therapy. We have recently shown that this sensitivity can be reversed, and resistance to PARP inhibition can be acquired by deletion of a mutation in BRCA2. Furthermore, a similar mechanism seems to be associated with carboplatin resistance in some BRCA2 mutation carriers with ovarian cancer.
携带突变型BRCA1或BRCA2基因的细胞在通过同源重组进行DNA修复方面存在缺陷，因此，它们对聚（ADP - 核糖）聚合酶（PARP）抑制剂高度敏感。这为一种新型的癌症治疗“合成致死”方法提供了基础。我们最近发现，这种敏感性可以被逆转，并且通过删除BRCA2中的一个突变可以获得对PARP抑制的抗性。此外，在一些患有卵巢癌的BRCA2突变携带者中，类似的机制似乎与卡铂耐药性有关。
