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0This research identifies lipid metabolism reprogramming as a critical driver of chemotherapy resistance in acute myeloid leukemia (AML). The study reveals that resistant leukemia cells survive by upregulating STAT3 signaling, which transcriptionally activates key regulators of lipid synthesis and oxidation, namely SREBP1 and CPT2. To combat this, researchers developed W1307, a highly selective STAT3 inhibitor that disrupts lipid homeostasis and induces lipotoxicity by causing an accumulation of toxic metabolic intermediates and oxidative stress. Experimental results demonstrate that W1307 effectively suppresses tumor growth and restores chemosensitivity to the standard drug Ara-C in both laboratory and animal models. Ultimately, these findings suggest that targeting the STAT3-mediated metabolic axis provides a promising therapeutic strategy for patients with advanced or drug-resistant leukemia.
References:
Peng K, Mo J, Yang Z, et al. Targeting STAT3-mediated lipid metabolism reprogramming overcomes chemoresistance in acute myeloid leukemia[J]. Cell Death & Disease, 2026.
