Journal of Cancer and Tumor International

Hepatocellular carcinoma (HCC) has significant gender differences in incidence and prognosis, indicating the sex-specific pathogenic process. Vitamin D₃, aside from its traditional function in calcium homeostasis, has pleiotropic actions with possible anti-cancer effects. This review discusses the therapeutic potential of vitamin D₃ in hepatocellular carcinoma, particularly its gender-dependent functions. Here we discuss the preclinical and clinical research on the differential effects of vitamin D₃ on hepatocellular carcinoma development and subsequent progression in male and female human subjects. Evidence suggests a modulation by the vitamin D₃ of sex hormone signalling, inflammatory processes, and immune responses in either gender, which in turn, affects hepatocarcinogenesis. Elucidating the sex-specific actions of vitamin D₃ has the promise of opening up targeted therapeutic approaches to perturb hepatocarcinogenesis. This review underscores the therapeutic potential of vitamin D₃ as a gender-sensitive drug in the treatment of hepatocellular carcinoma, that needs to be explored for future clinical applications.