Cancer ResearchHow Two Enzymes Hijack NAD Metabolism to Drive Cancer Resistance
Cancer cells are remarkably adaptable, and a new review explains a key reason why: two enzymes, NAMPT and NNMT, work in tandem to control how cells use nicotinamide — the building block of NAD+. NAMPT keeps intracellular NAD+ levels high, fueling energy production, DNA repair, and stress responses. NNMT diverts nicotinamide away from NAD+ synthesis and instead uses it to drain methyl groups, reshaping gene expression in ways that make tumors more plastic and harder to treat. Both enzymes also act outside the cell, influencing the tumor microenvironment, stromal remodeling, and immune evasion. Together they form a metabolic-epigenetic-immune network that helps tumors adapt to therapy. The review proposes targeting both enzymes simultaneously as a context-dependent strategy to overcome cancer resistance.
