The role of sirtuins in cancer progression

Abstract

Sirtuins represent a highly conserved family of nicotinamide adenine dinucleotide (NAD⁺)-dependent deacetylases that have emerged as pivotal regulators at the intersection of cellular metabolism, epigenetic regulation, and cancer biology. First identified as the mammalian orthologs of yeast Silent Information Regulator 2 (Sir2), the seven mammalian sirtuins (SIRT1–SIRT7) share a conserved catalytic core domain of approximately 275 amino acids yet exhibit remarkable functional diversity through distinct subcellular localizations, enzymatic activities, and substrate specificities. This evolutionary conservation from bacteria to mammals highlights their fundamental importance in cellular homeostasis and organismal survival. In the context of cancer, sirtuins have garnered substantial attention over the past two decades not merely as metabolic sensors, but as master regulators whose dysregulation profoundly influences tumor initiation, progression, and therapeutic response.