Crosstalk Between Metabolic Reprogramming and Epigenetic Modifications in Colorectal Cancer: Mechanisms and Clinical Applications.

Colorectal cancer (CRC) is one of the most common malignant tumors of the digestive tract in developing countries. It exhibits significant metabolic reprogramming and epigenetic abnormalities during its development. These two changes interact at the molecular level and jointly promote the progression of tumor cells. Cancer cells reprogram metabolites such as glucose, glutamine, and lipids to meet their energy and biological substrate requirements for survival. Concurrently, abnormalities in epigenetic modifications drive imbalances in gene expression and sustain the malignant phenotype. More importantly, metabolites can serve as substrates or cofactors for epigenetic enzymes, and changes in metabolic status can induce epigenetic remodeling. Correspondingly, epigenetic mechanisms regulate the transcription and function of metabolism-related genes, leading to adaptive alterations in tumor metabolic pathways. This review systematically summarizes the characteristics of major metabolic pathway reprogramming and the mechanisms underlying key epigenetic abnormalities in CRC. Furthermore, it elaborates on the mechanisms of their mutual influence in signaling pathways, key factors, immunometabolism, and the tumor microenvironment. It also discusses recent advances in novel diagnostic technologies (such as multi-omics integrated diagnostics) and therapeutic strategies (including targeting metabolism, epigenetic therapy, and combination therapies). In the future, research focusing on the interaction between metabolic reprogramming and epigenetics will provide new insights and targets for the early diagnosis and precision treatment of CRC.