Research Progress on Molecular Regulation and Targeted Therapy of Disulfidptosis
QI Xin1, LIU Tao1, NIE Fangfang2*, ZHU Guanghui1*
Disulfidptosis is a newly identified form of PCD (programmed cell death) caused by intracellular disulfide stress, with a unique molecular mechanism distinct from other PCD modalities such as apoptosis, pyroptosis, and ferroptosis. In this form of PCD, glucose deprivation in cells with high SLC7A11 expression leads to the depletion of NADPH. The resulting NADPH deficiency triggers abnormal disulfide cross-linking and collapse of the actin-dominated cytoskeletal network. The disulfidptosis pathway plays a pivotal role in disease pathogenesis and progression. Relevant studies have not only clarified that SLC7A11-high tumors exhibit a novel metabolic vulnerability, but also confirmed that targeting the disulfidptosis pathway in combination with ERS (endoplasmic reticulum stress) inhibitors exerts synergistic therapeutic effects. In addition, this pathway contributes to the progression of NAFLD (non-alcoholic fatty liver disease), and provides a novel theoretical basis for elucidating the immune escape mechanism of CD8⁺ T cell functional exhaustion mediated by LDHB (lactate dehydrogenase B) in the tumor microenvironment. Currently, various therapeutic strategies targeting this pathway have been proposed. Future research will further clarify its disease relevance and crosstalk with other types of programmed cell death, thereby laying a systematic theoretical foundation for the development of precision targeted therapies.
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