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Drug resistance mechanisms beyond DPP9-NRF2 (255) and AIM2-FOXO3a (258) are also underexploredwhether epigenetic modifications (e.g., DNA methylation of ACSL4), post-translational regulation (e.g., GPX4 ubiquitination), or metabolic rewiring (e.g., alternative antioxidant pathways) drives acquired resistance to ferroptosis inducers requires investigation

Upstream cysteine supply block, NADPH control, glutathione reductase activity repression, GSH efflux pumps stimulation, and so on have proven to be feasible approaches to ablate tumors (Xiong et al., 2021)

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