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定制卵巢癌治疗:突变的影响

Tailoring Ovarian Cancer Treatment: Implications of Mutations.

作者信息

Madariaga Ainhoa, Lheureux Stephanie, Oza Amit M

机构信息

Division of Medical Oncology & Hematology, Princess Margaret Cancer Center, Toronto, ON M5G 2M9, Canada.

出版信息

Cancers (Basel). 2019 Mar 23;11(3):416. doi: 10.3390/cancers11030416.

Abstract

High grade serous ovarian cancer (HGSOC) is the most common epithelial ovarian cancer, harbouring more than 20% germline or somatic mutations in the tumour suppressor genes and . These genes are involved in both DNA damage repair process via homologous recombination (HR) and transcriptional regulation. mutation confers distinct characteristics, including an increased response to DNA-damaging agents, such us platinum chemotherapy and poly-ADP ribose polymerase inhibitors (PARPi). However, several mechanisms of resistance to these agents have been described, including increased HR capacity through reverse mutations, non-homologous end-joint (NHEJ) repair alterations and drug efflux pumps. Current treatments of ovarian cancer including surgery, chemotherapy, targeted treatment and maintenance strategies, as well as resistance mechanisms will be reviewed, focusing on future trends with respect to mutation carriers.

摘要

高级别浆液性卵巢癌(HGSOC)是最常见的上皮性卵巢癌,肿瘤抑制基因和中存在超过20%的种系或体细胞突变。这些基因通过同源重组(HR)参与DNA损伤修复过程和转录调控。突变赋予了独特的特征,包括对DNA损伤剂(如铂类化疗药物和聚ADP核糖聚合酶抑制剂(PARPi))的反应增加。然而,已经描述了对这些药物的几种耐药机制,包括通过反向突变增加HR能力、非同源末端连接(NHEJ)修复改变和药物外排泵。将对卵巢癌的当前治疗方法(包括手术、化疗、靶向治疗和维持策略)以及耐药机制进行综述,重点关注携带突变者的未来趋势。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77a7/6468364/67bb75a5e1c8/cancers-11-00416-g001.jpg

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