Molecular Mechanisms of Mitochondrial Dynamics and Endoplasmic Reticulum Stress in Tumor Chemoresistance

doi:10.19803/j.1672-8629.20260249

Abstract

Abstract: Objective To explore the mechanisms of mitochondrial dynamics and endoplasmic reticulum stress in tumor chemoresistance so as to provide references for the development of clinical strategies for reversing drug resistance. Methods The key regulators of mitochondrial dynamics (fission and fusion) and their roles in drug resistance as well as the relationships between the three key pathways of the unfolded protein response (UPR) in endoplasmic reticulum stress (IRE1α, PERK, and ATF6) and chemoresistance were summarized based on literature review. Results Pharmacotherapy was one of the leading approaches to malignant tumors. However, the therapeutic efficacy was strongly limited by drug resistance. Mitochondria could regulate cellular metabolism, oxidative phosphorylation, and apoptotic thresholds through dynamic remodeling while endoplasmic reticulum stress could activate UPR pathways, collectively contributing to drug resistance. Conclusion Mitochondrial dynamics and endoplasmic reticulum stress are important mechanisms that mediate tumor chemoresistance, with close interactions between the two organelles through mitochondria-associated endoplasmic reticulum membranes (MAMs). Targeting key proteins involved in mitochondrial dynamics or modulating endoplasmic reticulum stress signaling pathways promises to be a novel strategy for reversing tumor drug resistance and improving chemotherapy efficacy.

Key words: Tumor, Drug Resistance, Mitochondrial Dynamics, Endoplasmic Reticulum Stress, Interaction, Mechanism

CLC Number:

GAO Zhichao, ZHAO Chenguang, FAN Youning, XUE Wenhan, LIANG Jingwei, WANG Lin, MENG Fanhao. Molecular Mechanisms of Mitochondrial Dynamics and Endoplasmic Reticulum Stress in Tumor Chemoresistance[J]. Chinese Journal of Pharmacovigilance, 2026, 23(6): 601-606.

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