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Modulation of redox homeostasis: A strategy to overcome cancer drug resistance
Yang Li1, Xiaoyue Zhang1, Zhihan Wang1
1State Key Laboratory of Biotherapy and Cancer Center, West China School of Basic Medical Sciences and Forensic Medicine, West China Hospital, and Collaborative Innovation Center for Biotherapy, Sichuan University, Chengdu, China.
Abstract:
Cancer treatment is hampered by resistance to conventional therapeutic strategies, including chemotherapy, immunotherapy, and targeted therapy. Redox homeostasis manipulation is one of the most effective innovative treatment techniques for overcoming drug resistance. Reactive oxygen species (ROS), previously considered intracellular byproducts of aerobic metabolism, are now known to regulate multiple signaling pathways as second messengers. Cancer cells cope with elevated amounts of ROS during therapy by upregulating the antioxidant system, enabling tumor therapeutic resistance via a variety of mechanisms. In this review, we aim to shed light on redox modification and signaling pathways that may contribute to therapeutic resistance. We summarized the molecular mechanisms by which redox signaling-regulated drug resistance, including altered drug efflux, action targets and metabolism, enhanced DNA damage repair, maintained stemness, and reshaped tumor microenvironment. A comprehensive understanding of these interrelationships should improve treatment efficacy from a fundamental and clinical research point of view.
Insights
Manipulating redox homeostasis, involving reactive oxygen species (ROS), is key to overcoming cancer drug resistance. Understanding ROS signaling mechanisms can improve cancer treatment efficacy.
Area of Science:
- Oncology
- Biochemistry
- Cellular Biology
Background:
- Cancer therapies like chemotherapy and immunotherapy often fail due to drug resistance.
- Reactive oxygen species (ROS) play crucial roles in cellular signaling and cancer progression.
- Cancer cells develop resistance by upregulating antioxidant systems to manage therapy-induced ROS.
Purpose of the Study:
- To review the role of redox modification and signaling in cancer therapeutic resistance.
- To elucidate molecular mechanisms underlying ROS-regulated drug resistance.
- To provide insights for improving fundamental and clinical cancer treatment strategies.
Main Methods:
- Literature review focusing on redox biology and cancer therapy.
- Analysis of molecular mechanisms of redox-regulated drug resistance.
- Synthesis of information on ROS signaling pathways in cancer.
Main Results:
- Redox signaling influences drug resistance through altered drug efflux, target modification, and metabolism.
- Enhanced DNA repair mechanisms and maintained cancer stemness contribute to resistance.
- The tumor microenvironment is reshaped by redox signaling, impacting treatment outcomes.
Conclusions:
- Redox homeostasis is a critical factor in cancer drug resistance.
- Targeting ROS signaling pathways presents a promising strategy for overcoming resistance.
- A comprehensive understanding of redox mechanisms is essential for advancing cancer therapy.
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