Rewiring of mitochondrial metabolism in therapy-resistant cancers: permanent and plastic adaptations

Frontiers in Cell and Developmental Biology

Cell and Developmental Biology

Katherine E. Pendleton¹  Gloria V. Echeverria¹  Karen Wang² 

[1] Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, United States;Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, United States;Department of Medicine, Baylor College of Medicine, Houston, TX, United States;Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, United States;Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, United States;Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, United States;Department of Medicine, Baylor College of Medicine, Houston, TX, United States;Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, United States;Department of BioSciences, Rice University, Houston, TX, United States;

关键词: metabolism;    cancer;    resistance;    plasticity;    oxphos (oxidative phosphorylation);   

DOI  :  10.3389/fcell.2023.1254313

 received in 2023-07-06, accepted in 2023-08-28,  发布年份 2023

来源: Frontiers

【 摘 要 】

Deregulation of tumor cell metabolism is widely recognized as a “hallmark of cancer.” Many of the selective pressures encountered by tumor cells, such as exposure to anticancer therapies, navigation of the metastatic cascade, and communication with the tumor microenvironment, can elicit further rewiring of tumor cell metabolism. Furthermore, phenotypic plasticity has been recently appreciated as an emerging “hallmark of cancer.” Mitochondria are dynamic organelles and central hubs of metabolism whose roles in cancers have been a major focus of numerous studies. Importantly, therapeutic approaches targeting mitochondria are being developed. Interestingly, both plastic (i.e., reversible) and permanent (i.e., stable) metabolic adaptations have been observed following exposure to anticancer therapeutics. Understanding the plastic or permanent nature of these mechanisms is of crucial importance for devising the initiation, duration, and sequential nature of metabolism-targeting therapies. In this review, we compare permanent and plastic mitochondrial mechanisms driving therapy resistance. We also discuss experimental models of therapy-induced metabolic adaptation, therapeutic implications for targeting permanent and plastic metabolic states, and clinical implications of metabolic adaptations. While the plasticity of metabolic adaptations can make effective therapeutic treatment challenging, understanding the mechanisms behind these plastic phenotypes may lead to promising clinical interventions that will ultimately lead to better overall care for cancer patients.

【 授权许可】

Unknown   
Copyright © 2023 Pendleton, Wang and Echeverria.