The role of redox homeostasis in tumor progression: implications for cancer therapy

The dynamic balance of reduction-oxidation (redox) plays a vital role in maintaining normal physiological functions, such as metabolism, cell differentiation, immune response, and cell death. The disruption of redox homeostasis in tumor cells leads to more adverse damage than that in normal tissues because of the significantly higher redox level resulting from the high metabolic characteristics of tumor tissue. However, tremendous efforts based on the regulation of redox homeostasis are still hampered by the enhanced antioxidant capability of tumor cells during treatment. Hence, an in-depth introduction regarding the relationship between tumors and oxidative stress, involving the factors leading to oxidative stress and the impact of oxidative stress on tumor progression, is urgently required for the development of cancer therapy strategies with robust antitumor effects. Thus, we systematically introduced the relationship between tumors and oxidative stress. We have also included another section to introduce the recent successes in the trial of oxidative stress-induced strategies based on nanomedicine. STATEMENT OF SIGNIFICANCE: Since cancer cells exhibit a unique, enhanced dynamic maintenance of redox homeostasis, this review is composed from a fresh perspective of the paradoxical crosstalk between redox homeostasis and tumor progression. We propose the disruption of redox balance acts as an intricate inducer for various forms of programmed cell death (PCD), including apoptosis, pyroptosis, ferroptosis, autophagy, cuproptosis, and disulfidptosis. Diverse strategies capable of amplifying oxidative stress for potent cancer treatment are subsequently summarized. The existing challenges together with the mitigation solutions are finally discussed. This review highlights the significant role of redox homeostasis in tumor progression, and is believed to bridge the gap between fundamental researches and clinical translations of nanomedicines developed in this research field.