PDF(Pubmed)
Abstract：
Ovarian cancer (OC) is the seventh most common cancer in women. Although women diagnosed with OC are usually treated frontline with platinum-based chemotherapy, most of them relapse once treatment is halted. Therefore, maintenance therapies have been developed to secure the response and delay further chemotherapy. There are two established maintenance therapies for women affected by platinum-sensitive recurrent OC: bevacizumab, a humanized monoclonal antibody targeting vascular endothelial growth factor, and olaparib, an inhibitor of poly (adenosine diphosphate [ADP]-ribose) polymerase (PARPi). Loss-of-function mutations in genes in the homologous recombination pathway, especially BRCA1 and BRCA2, predict higher rates of platinum sensitivity, better overall survival (OS), and better response to PARPi in women with OC. Among patients with platinum-sensitive recurrent OC, a BRCA mutation is the first genetically defined predictive marker for targeted therapy, since these patients are most likely to benefit from treatment with a PARPi, such as olaparib. In patients with platinum-sensitive recurrent OC without a BRCA mutation, bevacizumab currently seems to be the best maintenance option. Women with OC are progressively more routinely screened for germline BRCA mutations, and the implication of somatic BRCA mutations is increasingly being recognized in OC. Therefore, the recommendations should be updated to reflect the importance of both types of mutations. Together, these data highlight the fact that treatment of recurrent OC can be optimized using genomic contributions to individualize therapy and to improve treatment response.
摘要：
卵巢癌（OC）是女性第七大最常见的癌症。尽管诊断为OC的女性通常在一线接受铂类化疗，一旦治疗停止，他们中的大多数会复发。因此,已经开发了维持疗法以确保反应并延迟进一步的化疗。对于铂类敏感复发性OC患者，有两种既定的维持疗法：贝伐单抗，一种针对血管内皮生长因子的人源化单克隆抗体，还有奥拉帕利,聚(二磷酸腺苷[ADP]-核糖)聚合酶(PARPi)的抑制剂。同源重组途径中基因的功能缺失突变，特别是BRCA1和BRCA2，预测铂敏感率较高，更好的总体生存率（OS），对OC女性的PARPi反应更好。在铂类敏感复发性OC患者中，BRCA突变是靶向治疗的第一个基因定义的预测标记，由于这些患者最有可能从PARPi治疗中受益，比如奥拉帕利。在无BRCA突变的铂敏感复发性OC患者中，贝伐单抗目前似乎是最佳的维持方案.患有OC的女性逐渐更常规地筛查种系BRCA突变，体细胞BRCA突变的含义在OC中越来越被认识到。因此,应更新建议,以反映这两种突变的重要性.一起,这些数据凸显了这样一个事实,即复发性OC的治疗可以通过使用基因组贡献来优化,从而实现个体化治疗和改善治疗反应.
