Metabolic reprogramming and its implications for drug resistance in colorectal cancer

Abstract Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer-related deaths. Systemic therapy encounters substantial obstacles due to treatment resistance and reduced pharmacological effectiveness, yet it remains essential for intermediate and advanced CRC. Metabolic reprogramming is a crucial element that contributes to treatment resistance and has attracted much interest. Cells modify their metabolism to satisfy energy requirements, adjust to growth needs, or withstand environmental stressors. To comprehend the initiation, progression, and treatment resistance of CRC, it is essential to understand the expression of metabolic enzymes and the interplay of metabolic pathways. Examining metabolic reprogramming and its related pathways is critical for advancing CRC treatment. The solution to these problems is utilizing inhibitors to target metabolic enzymes precisely. In advanced CRC, inhibitors utilized alongside systemic treatment drugs can reduce drug resistance and improve overall survival. This review elucidates the role of metabolic reprogramming in colorectal cancer progression and chemotherapy resistance, explores therapeutic strategies targeting metabolism, and summarizes research progress on inhibitors targeting key metabolic nodes, providing new perspectives for mechanistic research and clinical treatment.