《生命科学》 2022, 34(8): 1010-1017

mTOR抑制剂在肾细胞癌中的应用及其耐药机制

谭志林 , 车文安 , 陈　巍^*

深圳大学第一附属医院，深圳市第二人民医院，深圳 518036

摘　要：

肾细胞癌(renal cell carcinoma, RCC) 对传统的化疗和放疗普遍耐受，靶向疗法的出现为RCC 患者提供了一种新的治疗方案。哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin, mTOR) 形成两种多亚基复合物：mTOR 复合物1 (mTOR complex 1, mTORC1) 和mTOR 复合物2 (mTOR complex 2, mTORC2)，其参与的PI3K/Akt/mTOR 通路在细胞生长和代谢中起重要作用。许多肿瘤中都有mTOR 信号通路的改变，肾细胞癌中也常出现该通路的异常激活，因此mTOR 是治疗晚期肾细胞癌的重要靶点。目前针对肾细胞癌存在以mTOR 为靶点的几类mTOR 抑制剂，但这些药物的使用常有耐药现象发生。该文综述了肾细胞癌中PI3K/Akt/mTOR 通路的改变，以及mTOR 抑制剂的发展和相应的耐药机制，可为肾细胞癌患者用药提供一定参考，促进相关通路的药物研发。

通讯作者：陈　巍 , Email:jessie_chenwei@163.com

Application and resistant mechanism of mTOR inhibitor in renal cell carcinoma

TAN Zhi-Lin , CHE Wen-An , CHEN Wei^*

First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen 518036, China

Abstract:

Renal cell carcinoma is generally resistant to conventional chemotherapy and radiotherapy, but the emergence of targeted therapies offers a new treatment option for patients with RCC. mTOR (mammalian target of rapamycin) proteins form two multisubunit complexes: the mTOR complex 1(mTORC1) and mTOR complex 2 (mTORC2), which are involved in the PI3K/Akt/mTOR pathway and play vital roles in cell growth and metabolism. Alterations in the mTOR signaling pathway occur in many tumors, and abnormal activation of this pathway is also common in renal cell carcinoma. Therefore, mTOR is a vital target for the treatment of advanced renal cell carcinoma. Several mTOR inhibitors that target mTOR are currently used in renal cell carcinoma, but the use of these drugs often results in resistance. Therefore, this article reviews the changes of PI3K/Akt/mTOR pathway in renal cell carcinoma, as well as the development of mTOR inhibitors and corresponding mechanisms of drug resistance, which can provide some reference for the medication of patients with renal cell carcinoma and promote the drug development targeting related pathways.

Communication Author：CHEN Wei , Email:jessie_chenwei@163.com