Epigenetics and One-Carbon Metabolism in Cancer: Mechanisms and Therapeutic Implications

Epigenetics refers to heritable changes in gene expression that occur without alterations in the DNA sequence itself, primarily through mechanisms such as DNA methylation and histone modifications. These regulatory processes are essential for normal development, cellular differentiation, and genome stability. In cancer, however, epigenetic reprogramming becomes dysregulated, contributing to tumor initiation, progression, and metastasis. Aberrant DNA methylation patterns and histone modifications can silence tumor suppressor genes or activate oncogenes, driving malignant transformation. Central to these epigenetic processes is one-carbon metabolism-a biochemical network that supplies methyl groups for DNA and histone methylation through metabolites such as S-adenosylmethionine (SAM). As such, the interplay between one-carbon metabolism and epigenetic regulation is a critical axis in understanding and potentially targeting cancer biology.