As a pivotal hub of cellular metabolism, NAD + metabolic reprogramming exerts a core role in colorectal cancer chemoresistance by regulating energy metabolism, DNA repair, and the immune microenvironment. The dysregulation of synthetic and catabolic pathways mediated by key molecules such as NAMPT, SIRT1, and PARP constitutes a crucial mechanism underlying chemoresistance development. Targeted intervention strategies against NAD + metabolism, including precursor supplementation, inhibitor administration, and combination therapy, have exhibited remarkable anti-cancer potential and represent promising translational strategies for reversing chemoresistance. However, clinical translation of these strategies is severely impeded by tumor metabolic heterogeneity, the lack of dynamic NAD + monitoring technologies and insufficient tissue specificity of targeted drugs. By leveraging emerging techniques including multi-omics integration, organoid models, nano-delivery systems, and dynamic imaging, in-depth dissection of metabolic heterogeneity and development of personalized intervention regimens can provide novel and effective avenues to overcome the predicament of colorectal cancer chemoresistance, which holds important translational research value and clinical application significance.
Ma et al. (Thu,) studied this question.