Glucose starvation mimetic aldometanib removes immune barriers permitting mice with hepatocellular carcinoma to live to normal ages.

ABSTRACT: Dysregulated metabolism in tumor tissues and para-tumor tissues alike can lead to immunosuppression, which may underlie cancer development. However, metabolic intervention as a therapeutic strategy has been of no avail. In this study, we explored the anti-cancer therapeutic effect of aldometanib, which specifically targets lysosome-associated aldolase to mimic glucose starvation and thereby activates lysosomal AMP-activated protein kinase (AMPK), a master regulator of metabolic homeostasis. We show that aldometanib inhibits the growth of hepatocellular carcinoma (HCC) in an AMPK-dependent manner, allowing hepatoma-bearing mice to survive to mature ages, although aldometanib does not possess cytotoxicity toward HCC or normal cells. Intriguingly, aldometanib exerts anti-cancer effects only i

SUBMITTER: Hu HH 

PROVIDER: S-EPMC12690099 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature