卵巢癌微环境与化疗耐药发生相关的研究进展

Progress in microenvironment and chemoresistance of ovarian cancer

卵巢癌发病率位居女性生殖系统肿瘤的第3位,但其致死率在妇科肿瘤中最高。目前,卵巢癌标准一线治疗方案为肿瘤减灭术辅以铂类联合紫杉醇化疗。尽管患者在治疗初期可获得较为明显的效果,初次治疗缓解率高,但大多数患者在完全缓解2年左右会复发,复发率高达80%。复发性上皮卵巢癌患者几乎对所有化疗药物产生抗性,多药耐药的产生是卵巢癌治疗失败的主要原因。因此,揭示卵巢癌耐药的分子机制是亟待解决的问题之一。近年来,肿瘤微环境概念的提出为研究肿瘤的发生、发展和耐药等机制提供了一个全新的整体视角。卵巢癌具有自身独特的肿瘤微环境,后者影响免疫监视,并介导化疗抵抗。因此从卵巢癌微环境的角度解释卵巢癌化疗耐药的相关机制有助于寻找有效逆转卵巢癌耐药的靶点。本文首先介绍卵巢癌耐药和卵巢癌微环境的一般概况,然后重点综述近几年来卵巢癌微环境中各种组分与耐药相关的研究进展,旨在从微环境角度解释卵巢癌耐药发生的机制,并寻找微环境中的有效靶点用以解决临床耐药难题;最后对卵巢癌微环境与耐药的未来研究方向进行展望。

Among all gynecological tumors,ovarian cancer is the third most common cancer but the most lethal one.Currently,the standard first-line treatment for ovarian cancer is cytoreductive surgery combined with platinum and paclitaxel chemotherapy.Although the patients with ovarian cancer respond to the standard therapeutic approach and gain a high remission rate,the most patients relapse after about 2 years of complete remission,the recurrence rate is as high as 80%.The patients with recurrent epithelial ovarian cancer are resistant to almost all chemotherapy drugs due to the acquired resistance.Multidrug resistance to chemotherapy is a major cause of treatment failure.Therefore,it is an urgent problem to reveal the molecular mechanism of ovarian cancer resistance.In recent years,tumor microenvironment as an emerge concept has provided a new perspective for the study of tumorigenesis,progression and drug-resistance.Ovarian cancer is characterized by a unique tumor microenvironment that impairs immune surveillance and mediates therapy resistance.Explaining the mechanism of chemotherapy resistance from the perspective of ovarian cancer microenvironment is helpful to find effective targets reversing the drug resistance of ovarian cancer.This review first introduces the general situation of drug resistance and microenvironment of ovarian cancer,and then focuses on the research progress in the relationship of various components of ovarian cancer microenvironment with drug resistance,in order to explain the occurrence mechanisms of ovarian cancer resistance and find effective targets in the microenvironment to solve the problem of clinical drug resistance.In the end,the forward research directions in this field are prospected in this review.