Glycolytic reprogramming in precancerous lesions of gastric cancer progression: pathogenesis and therapeutic...

Precancerous lesions of gastric cancer (PLGC) represent a critical stage preceding the development of gastric cancer. Their progression to gastric cancer remains a significant challenge in clinical prevention and treatment. Recent studies have shown that glycolytic reprogramming is a dynamic and modifiable metabolic process in PLGC. It may emerge during the progression of PLGC and contribute to the pathological remodeling of the gastric mucosa. This article reviews the stage-specific characteristics, pathogenesis, and therapeutic potential of glycolytic reprogramming in PLGC. During the progression of PLGC, glycolytic activity may be activated early on, diminish during the glandular atrophy stage, and be reactivated during intestinal metaplasia (IM), dysplasia, and spasmolytic polypeptide-expressing metaplasia (SPEM). Key regulatory factors include Helicobacter pylori (H. pylori) infection, the PI3K/Akt/mTOR-HIF-1α axis, glucose uptake mediated by glucose transporters (GLUTs), microRNAs (miRNAs), the p53/TIGAR pathway, and p57. These metabolic alterations may promote PLGC progression through an imbalance between proliferation and apoptosis, lactate accumulation, and the formation of an acidic microenvironment. Intervention strategies targeting glycolytic reprogramming may offer potential approaches for metabolic intervention in PLGC. These strategies include traditional Chinese medicine formulations, natural bioactive compounds, and glycolysis inhibitors derived from gastric cancer research.