Homologous Recombination Deficiency: Exploiting the Fundamental Vulnerability of Ovarian Cancer.
Homologous Recombination Deficiency: Exploiting the Fundamental Vulnerability of Ovarian Cancer.
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DOI：
10.1158/2159-8290.cd-15-0714
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发表时间：
2015-11
期刊：
影响因子：
28.2
通讯作者：
D'Andrea AD
中科院分区：
文献类型：
--
作者：
Konstantinopoulos PA;Ceccaldi R;Shapiro GI;D'Andrea AD
大约50%的上皮性卵巢癌（EOC）表现出通过同源重组（HR）的缺陷DNA修复，这是由于HR途径基因的遗传和表观遗传改变。缺陷HR是EOC中的重要治疗靶点，如铂类似物在该疾病中的功效以及聚ADP核糖聚合酶抑制剂的出现所例证的，所述聚ADP核糖聚合酶抑制剂在应用于HR缺陷细胞时表现出合成致死性。在这里，我们描述了HR缺陷EOCs的基因型和表型特征，讨论了当前和新兴的靶向这些肿瘤的方法，并提出了与这些方法相关的挑战，重点是发展和克服耐药性。
Approximately 50% of epithelial ovarian cancers (EOCs) exhibit defective DNA repair via homologous recombination (HR) due to genetic and epigenetic alterations of HR pathway genes. Defective HR is an important therapeutic target in EOC as exemplified by the efficacy of platinum analogues in this disease, as well as the advent of poly-ADP ribose polymerase inhibitors which exhibit synthetic lethality when applied to HR deficient cells. Here, we describe the genotypic and phenotypic characteristics of HR deficient EOCs, discuss current and emerging approaches for targeting these tumors, and present challenges associated with these approaches focusing on development and overcoming resistance.