Metabolic Reprogramming in Gallbladder Cancer

Gallbladder cancer (GBC) is a rare but highly aggressive malignancy with a poor prognosis, characterized by late detection and rapid progression. Despite its relatively low global incidence, GBC accounts for a disproportionately high number of cancer-related deaths. A key driver of its malignancy is metabolic reprogramming, wherein cancer cells alter their energy production pathways to support uncontrolled growth and survival. This review delves into the metabolic shifts in GBC cells, with a focus on glucose metabolism, lipid biosynthesis, and protein utilization. The Warburg effect, a hallmark of cancer metabolism, promotes aerobic glycolysis over oxidative phosphorylation in GBC cells, with circβ-catenin and circFOXP1 playing pivotal roles in this shift. Lipid metabolism is also reprogrammed, with circEZH2 contributing to increased lipid synthesis and storage. Protein metabolism is upregulated via the mTOR pathway, enhancing protein synthesis and amino acid utilization to support tumor growth. Targeting these metabolic pathways offers potential therapeutic strategies to hinder GBC progression and improve patient outcomes.