The development of cancers research based on mitochondrial heat shock protein 90

Yuchu Xiang; Xudong Liu; Qi Sun; Kuo Liao; Xiaohan Liu; Zihui Zhao; Lishuang Feng; Yan Liu; Bo Wang

doi:10.3389/fonc.2023.1296456

The development of cancers research based on mitochondrial heat shock protein 90

Front Oncol. 2023 Nov 30:13:1296456. doi: 10.3389/fonc.2023.1296456. eCollection 2023.

Authors

Yuchu Xiang^#¹, Xudong Liu^#², Qi Sun^#³, Kuo Liao⁴, Xiaohan Liu⁵, Zihui Zhao⁶, Lishuang Feng⁷, Yan Liu⁸, Bo Wang^{2

9}

Affiliations

¹ West China Hospital of Sichuan University, Sichuan University, Chengdu, China.
² Institute of Medical Microbiology and Hygiene, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
³ Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, Centre for Safe Medication Practice and Research, The University of Hong Kong, Pok Fu Lam, Hong Kong SAR, China.
⁴ School of Biology and Biological Engineering, South China University of Technology, Guangzhou, China.
⁵ Multiscale Research Institute of Complex Systems, Fudan University, Shanghai, China.
⁶ Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁷ School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, China.
⁸ Department of Organ Transplantation, Guizhou Provincial People's Hospital, Guiyang, Guizhou, China.
⁹ Department of Urology, Guizhou Provincial People's Hospital, Guiyang, Guizhou, China.

^# Contributed equally.

Abstract

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.

Keywords: TRAP1; gamitrinib; mitochondria; molecular chaperone; mtHsp90.

Publication types

Review

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. BW is supported by China Scholarship Council (CSC).