ALDOA-Mediated Metabolic Reprogramming is a Targetable Vulnerability for Ferroptosis Sensitization in Cancer.

ABSTRACT: Ferroptosis presents great potential for cancer therapy, either alone or in combination with classical therapy. However, inducing ferroptosis by targeting canonical ferroptosis suppressors that directly inhibit lipid peroxidation non-selectively induces ferroptosis in both cancerous and normal cells, thereby limiting its therapeutic potential. In this study, it is revealed that aldolase A (ALDOA) reprograms lipid metabolism to resist ferroptosis in cancer cells and identifies ALDOA as a targetable vulnerability for ferroptosis sensitization. Cancer cells with ALDOA suppression exhibit increased susceptibility to ferroptosis-a response less obvious in normal cells. Mechanistically, ALDOA depletion induces significant accumulation of fructose 1,6-bisphosphate in cancer cells, thereby enhanci

SUBMITTER: Wang P 

PROVIDER: S-EPMC12866770 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature