Cancer Metabolism Meets DNA Repair: The Hidden Link to Therapy Resistance

Cancer cells exhibit reprogrammed metabolic pathways to sustain aggressive phenotypes, including continuous cell division, stemness, invasion, and metastasis. Emerging evidence suggests that these metabolic adaptations profoundly impact DNA repair pathways, which contribute to the responses to therapy and influence overall outcomes. Metabolic processes such as the Warburg effect, nicotinamide adenine dinucleotide (NAD) metabolism, glutamine metabolism, and one-carbon metabolism support DNA repair by expanding the metabolite pool and facilitating post-translational modifications. Conversely, oncometabolites impair DNA repair pathways through epigenetic reprogramming, thereby promoting genomic instability. This review highlights recent discoveries that elucidate the intricate connections between metabolic hallmarks in cancer cells and DNA repair mechanisms, offering insights into potential therapeutic targets for future cancer treatments.