Vitamin D₃ in cancer prevention and therapy: molecular mechanisms, clinical evidence, and future perspectives.

Vitamin D3, also known as cholecalciferol, is a fat-soluble secosteroid that plays a critical role in regulating calcium and phosphate homeostasis and supporting bone health. Recent studies have highlighted its broad physiological and therapeutic applications, with particular focus on its anticancer properties. Vitamin D3, through its active metabolite calcitriol, mediates a wide range of biological effects by modulating key cellular processes, including proliferation, differentiation, apoptosis, and angiogenesis. It is produced cutaneously after ultraviolet B exposure or obtained from dietary sources and then undergoes sequential hydroxylation in the liver and kidneys to form its biologically active compound. This review delineates the molecular underpinnings of vitamin D3 in cancer biology, emphasizing the interplay between genomic and non-genomic signaling pathways that collectively orchestrate tumor initiation and progression. Clinical evidence indicates that D3 supplementation shows promising therapeutic benefits as an adjunct to conventional cancer treatment, particularly in patients with vitamin D deficiency, although findings remain inconsistent across cancer types and clinical settings. Overall, current evidence supports vitamin D₃ as a safe, cost-effective, and promising adjuvant strategy in oncology; however, its routine clinical application requires validation through well-designed, large-scale randomized controlled trials to establish optimal dosing strategies, identify responsive patient populations, and confirm long-term efficacy and safety.