卵巢癌耐药机制与靶向治疗策略的研究进展

Research progress of drug resistance in ovarian cancer and targeted therapy strategy

手术结合化疗是卵巢上皮性癌的主要治疗手段,其中以R0为目标的卵巢癌肿瘤细胞减灭术结合个体化的化疗方案的应用,使得部分患者5年生存率有了很大的提升。但是晚期患者的耐药与复发仍然是困扰广大临床医师与科研工作者的难题,而化疗耐药因其病因不清、机制复杂,是临床亟待解决的难题和热点。近年来围绕此问题开展的基础与临床相结合的卵巢癌耐药的机制研究主要包括药物转运、药物代谢、细胞凋亡、DNA损伤修复、表观遗传学改变等,细胞自噬、肿瘤代谢、肿瘤微环境及肿瘤干细胞等在卵巢癌耐药方面也发挥了重要作用,针对耐药机制的靶向药物治疗为提高化疗敏感性、改善患者预后提供了新的思路。

Cytoreductive surgery combined with chemotherapy is the major treatment of Epithelial ovarian cancer(EOC). The application of no residual disease(R0) targeted ovarian cancer debulking with individualized chemotherapy has greatly improved the five-year survival rates. However, the drug resistance and recurrence of advanced patients are still a difficult problem for clinicians and researchers in this field. Chemotherapy resistance is a hot and difficult spot to be solved urgently due to unclear etiology and complex mechanism. In recent years, the basic and clinical researches on the mechanism of drug resistance in ovarian cancer mainly include drug transport, drug metabolism, apoptosis, DNA damage repair and epigenetic changes. And some studies have shown that autophagy, altered metabolism, tumor microenvironment and tumor stem cells also have played an important role in drug resistance in ovarian cancer. The strategy targeting these mechanisms has provided a new method to increase sensitivity to chemotherapy and improve the prognosis.