Review Article

Chemotherapy-induced metastasis: molecular mechanisms and clinical therapies

Jin-xuan Su1,2,3, Si-jia Li1,2,3, Xiao-feng Zhou1,2,3, Zhi-jing Zhang1,2,3, Yu Yan4, Song-lin Liu5, Qi Qi1,2,3
1 State Key Laboratory of Bioactive Molecules and Druggability Assessment
2 MOE Key Laboratory of Tumor Molecular Biology
3 Department of Pharmacology, School of Medicine, Jinan University, Guangzhou 510632, China
4 Functional Experimental Teaching Center, School of Medicine, Jinan University, Guangzhou 510632, China
5 Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, China
Correspondence to: Yu Yan: yanyu@jnu.edu.cn, Song-lin Liu: songlinsteven@qq.com, Qi Qi: qiqikc@jnu.edu.cn,
DOI: 10.1038/s41401-023-01093-8
Received: 20 February 2023
Accepted: 11 April 2023
Advance online: 11 May 2023

Abstract

Chemotherapy, the most widely accepted treatment for malignant tumors, is dependent on cell death induced by various drugs including antimetabolites, alkylating agents, mitotic spindle inhibitors, antitumor antibiotics, and hormonal anticancer drugs. In addition to causing side effects due to non-selective cytotoxicity, chemotherapeutic drugs can initiate and promote metastasis, which greatly reduces their clinical efficacy. The knowledge of how they induce metastasis is essential for developing strategies that improve the outcomes of chemotherapy. Herein, we summarize the recent findings on chemotherapy-induced metastasis and discuss the underlying mechanisms including tumor-initiating cell expansion, the epithelial-mesenchymal transition, extracellular vesicle involvement, and tumor microenvironment alterations. In addition, the use of combination treatments to overcome chemotherapy-induced metastasis is also elaborated.
Keywords: anti-cancer drugs; chemotherapy; metastasis; combination therapy

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