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Bcl-2 家族:卵巢癌个体化治疗的新视角(综述)。

Bcl‑2 family: Novel insight into individualized therapy for ovarian cancer (Review).

机构信息

Department of Gynecology and Obstetrics, Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China.

出版信息

Int J Mol Med. 2020 Oct;46(4):1255-1265. doi: 10.3892/ijmm.2020.4689. Epub 2020 Jul 29.

Abstract

Chemoresistance to platinum‑based chemotherapy for ovarian cancer in the advanced stage remains a formidable concern clinically. Increasing evidence has revealed that apoptosis represents the terminal events of the anti‑tumor mechanisms of a number of chemical drugs and has a close association with chemoresistance in ovarian cancer. The B‑cell lymphoma‑2 (Bcl‑2) family plays a crucial role in apoptosis and has a close association with chemoresistance in ovarian cancer. Some drugs that target Bcl‑2 family members have shown efficacy in overcoming the chemoresistance of ovarian cancer. A BH3 profiling assay was found to be able to predict how primed a cell is when treated with antitumor drugs. The present review summarizes the role of the Bcl‑2 family in mediating cell death in response to antitumor drugs and novel drugs that target Bcl‑2 family members. The application of the new functional assay, BH3 profiling, is also discussed herein. Furthermore, the present review presents the hypothesis that targeting Bcl‑2 family members may prove to be helpful for the individualized therapy of ovarian cancer in clinical practice and in laboratory research.

摘要

在晚期卵巢癌中,对铂类化疗药物的耐药性仍然是临床上令人担忧的问题。越来越多的证据表明,细胞凋亡代表了多种化学药物抗肿瘤机制的终末事件,与卵巢癌的耐药性密切相关。B 细胞淋巴瘤-2(Bcl-2)家族在细胞凋亡中发挥着关键作用,与卵巢癌的耐药性密切相关。一些针对 Bcl-2 家族成员的药物已显示出在克服卵巢癌耐药性方面的疗效。BH3 谱分析被发现能够预测细胞在用抗肿瘤药物治疗时的预激程度。本综述总结了 Bcl-2 家族在介导细胞对抗肿瘤药物的死亡反应中的作用,以及针对 Bcl-2 家族成员的新型药物。本文还讨论了新的功能测定方法 BH3 谱分析的应用。此外,本综述提出了一种假设,即靶向 Bcl-2 家族成员可能有助于卵巢癌的个体化治疗,这在临床实践和实验室研究中都具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44a5/7447322/aadfc31f71f8/IJMM-46-04-1255-g00.jpg

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