Targeting Metabolic–Redox Nexus to Regulate Drug Resistance: From Mechanism to Tumor Therapy
Yuke Wang,
Jingqiu He,
Shan Lian,
Yan Zeng,
Sheng He,
Jue Xu,
Li Luo,
Wenyong Yang,
Jingwen Jiang
Affiliations
Yuke Wang
West China School of Public Health and West China Fourth Hospital, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, China
Jingqiu He
West China School of Public Health and West China Fourth Hospital, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, China
Shan Lian
West China School of Public Health and West China Fourth Hospital, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, China
Yan Zeng
West China School of Public Health and West China Fourth Hospital, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, China
Sheng He
West China School of Public Health and West China Fourth Hospital, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, China
Jue Xu
West China School of Public Health and West China Fourth Hospital, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, China
Li Luo
Center for Reproductive Medicine, Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu 610041, China
Wenyong Yang
Department of Neurosurgery, Medical Research Center, The Third People’s Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, The Second Chengdu Hospital Affiliated to Chong-Qing Medical University, Chengdu 610041, China
Jingwen Jiang
West China School of Public Health and West China Fourth Hospital, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, China
Drug resistance is currently one of the biggest challenges in cancer treatment. With the deepening understanding of drug resistance, various mechanisms have been revealed, including metabolic reprogramming and alterations of redox balance. Notably, metabolic reprogramming mediates the survival of tumor cells in harsh environments, thereby promoting the development of drug resistance. In addition, the changes during metabolic pattern shift trigger reactive oxygen species (ROS) production, which in turn regulates cellular metabolism, DNA repair, cell death, and drug metabolism in direct or indirect ways to influence the sensitivity of tumors to therapies. Therefore, the intersection of metabolism and ROS profoundly affects tumor drug resistance, and clarifying the entangled mechanisms may be beneficial for developing drugs and treatment methods to thwart drug resistance. In this review, we will summarize the regulatory mechanism of redox and metabolism on tumor drug resistance and highlight recent therapeutic strategies targeting metabolic–redox circuits, including dietary interventions, novel chemosynthetic drugs, drug combination regimens, and novel drug delivery systems.
