Xiang Yuchu, Liu Xudong, Sun Qi, Liao Kuo, Liu Xiaohan, Zhao Zihui, Feng Lishuang, Liu Yan, Wang Bo
West China Hospital of Sichuan University, Sichuan University, Chengdu, China.
Institute of Medical Microbiology and Hygiene, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Front Oncol. 2023 Nov 30;13:1296456. doi: 10.3389/fonc.2023.1296456. eCollection 2023.
Mitochondrial heat shock protein 90 (mtHsp90), including Tumor necrosis factor receptor-associated protein 1 (TRAP1) and Hsp90 translocated from cytoplasm, modulating cellular metabolism and signaling pathways by altering the conformation, activity, and stability of numerous client proteins, and is highly expressed in tumors. mtHsp90 inhibition results in the destabilization and eventual degradation of its client proteins, leading to interference with various tumor-related pathways and efficient control of cancer cell development. Among these compounds, gamitrinib, a specific mtHsp90 inhibitor, has demonstrated its safety and efficacy in several preclinical investigations and is currently undergoing evaluation in clinical trials. This review aims to provide a comprehensive overview of the present knowledge pertaining to mtHsp90, encompassing its structure and function. Moreover, our main emphasis is on the development of mtHsp90 inhibitors for various cancer therapies, to present a thorough overview of the recent pre-clinical and clinical advancements in this field.
线粒体热休克蛋白90(mtHsp90),包括肿瘤坏死因子受体相关蛋白1(TRAP1)和从细胞质转位而来的Hsp90,通过改变众多客户蛋白的构象、活性和稳定性来调节细胞代谢和信号通路,并且在肿瘤中高表达。mtHsp90抑制导致其客户蛋白的不稳定并最终降解,从而干扰各种肿瘤相关途径并有效控制癌细胞的发展。在这些化合物中,特异性mtHsp90抑制剂加米替尼已在多项临床前研究中证明了其安全性和有效性,目前正在进行临床试验评估。本综述旨在全面概述目前关于mtHsp90的知识,包括其结构和功能。此外,我们主要关注用于各种癌症治疗的mtHsp90抑制剂的开发,以全面概述该领域最近的临床前和临床进展。