EXPRESS: Vitamin D and cancer connection: Is it a promise for cancer Prevention?

Traditionally, vitamin D has been recognized primarily for its role in regulating calcium homeostasis and supporting skeletal integrity. Current research has found growing evidences of other biological processes involving vitamin D that contribute to cancer etiology and pathogenesis. Recently, increasing scientific attention has focused on the potential protective role of vitamin D against cancer, mediated through its regulation of cellular proliferation and differentiation, modulation of immune responses, and inhibition of metastatic processes. Current scientific interest in this area is substantial due to the high prevalence of vitamin D deficiency, even in populations with sufficient sunlight exposure and supplement intake, alongside the global rise in cancer incidence. A key research challenge is to elucidate the potential association between vitamin D deficiency and increased cancer risk through critical evaluation of existing literature, which often presents inconsistent and conflicting findings.This narrative literature review aims to synthesize the existing evidence on the relationship between vitamin D and cancer, with particular emphasis on VDR-mediated molecular mechanisms involved in carcinogenesis, including antiproliferative and anti-metastatic actions, as well as modulation of immune system responses. In contrast to the bulk of previous studies aimed at either epidemiological assessment or elucidation of molecular pathways, the considered study attempted to combine these two approaches. According to the available information, vitamin D can influence tumor biology through several possible mechanisms such as regulation of the cell cycle, inhibition of epithelial-to-mesenchymal transition, regulation of the tumor microenvironment, and modulation of inflammation. Nevertheless, although the proposed use of vitamin D in cancer therapy appears biologically plausible based on current mechanistic evidence, it remains unjustified at this stage due to insufficient clinical support for its efficacy. Clinicians should acknowledge that while the underlying biological rationale is compelling, existing evidence does not currently substantiate the use of vitamin D as a therapeutic intervention for cancer.