Targeting AKR1B1 inhibits metabolic reprogramming to reverse systemic therapy resistance in hepatocellular carcinoma.

ABSTRACT: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, and resistance to systemic therapies remains a significant clinical challenge. This study investigated the mechanisms by which metabolic reprogramming contributes to systemic treatment resistance in HCC. We established HCC cell lines with multidrug resistance characteristics and observed enhanced metabolic activity in these cells. Integrated multiomics analyses revealed hyperactive glucose‒lipid and glutathione metabolic pathways that play critical roles in supporting tumor cell proliferation and survival. We constructed a metabolic reprogramming atlas for HCC-resistant cells and identified aldo-keto reductase (Aldo-keto reductase family 1 Member B1, AKR1B1) as a key regulator of this reprogramming, which sustai

SUBMITTER: Wang Q 

PROVIDER: S-EPMC12317016 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature