Disulfidptosis and its molecular mechanisms in cancer: mechanisms, regulation, and therapeutic potential.

Disulfidptosis is a novel form of programmed cell death. It is triggered by metabolic and redox imbalance. It is executed through the irreversible collapse of the actin cytoskeleton. Its core mechanism involves the 'SLC7A11-cystine-NADPH-actin axis'. This process selectively kills cancer cells while sparing normal cells. This provides a new direction for low-toxicity anticancer therapy. This review systematically summarizes the multi-layered molecular regulatory network governing disulfidptosis. It elucidates the underlying mechanisms through several lenses. These include metabolic reprogramming (glucose metabolism, pentose phosphate pathway, cystine uptake), redox homeostasis (reactive oxygen species (ROS), glutathione system, thioredoxin system), cytoskeletal dynamics, and key signaling pathways such as Keap1-Nrf2, AMPK, and p53. The review clarifies its dual role in tumors. Cancer cells exhibit specific susceptibility due to metabolic reprogramming. Cells resistant to apoptosis or ferroptosis show heightened vulnerability. This stems from a 'fragile redox equilibrium'. However, functional polarity reversal of core regulatory molecules and tumor heterogeneity can also impact therapeutic efficacy. Targeting key molecules in disulfidptosis or combining metabolic interventions shows promising anticancer potential. However, current research still faces bottlenecks. These include unclear heterogeneity mechanisms and a lack of highly specific tools. Future efforts should establish precise classification systems, develop targeted drugs, and explore synergistic strategies combining immunotherapy to promote clinical translation.