Targeting Folate Metabolism for Cancer Drug Development

Folate, also known as folic acid (FA), is an essential nutrient widely used as a dietary supplement. The association of FA with cancer risk has been extensively studied, yet the underlying mechanisms remain complex and context dependent. This review examines the role of folate metabolism in cancer pathogenesis, with a focus on the particular influence of FA on cancer initiation, proliferation, migration, and progression. We discuss how folate modulates key signaling pathways involved in cell proliferation and migration, and how folate metabolism-related genes directly affect cancer progression. Furthermore, we highlight recent advances in therapeutic strategies that leverage folate pathways, including folate receptor-targeted antibody–drug conjugates (ADCs), folate–nanoparticle conjugates, and folate–polymer-based antitumor agents. Collectively, these insights underscore folate metabolism and folate receptors as promising targets for the design and development of novel anticancer drugs. Further in vivo and in vitro studies are warranted to elucidate the precise relationship between folate status and cancer dynamics.