The number of known biological activities of vitamin D is has increased exponentially in recent years. Currently, vitamin D is implicated in the treatment of various chronic diseases including cancer, diabetes, and cardiovascular ailments. Several epidemiological studies have revealed low vitamin D levels in patients suffering from cancers and recent investigations have demonstrated the ability of vitamin D supplemented diets to reduce tumor burden in animal models. However, it is still unclear whether such dietary intervention reduces the burden of cancers in humans. Therefore, it is important to conduct studies to determine whether dietary supplementation reduces tumor growth. Several in vitro studies and preclinical data have delineated the molecular mechanisms by which vitamin D induces death signaling cascades in cancer cells. Mechanistically, vitamin D induces G0/G1 arrest, apoptotic cascades, and inhibits angiogenesis and proliferation of cells by targeting key signaling cascades in cancer cells. Molecularly, vitamin D modulates the expression of genes by altering the levels of microRNAs thereby upregulating tumor suppressor/apoptotic proteins while downregulating oncogenic molecules.

However, in-depth studies are still needed to identify miRNA signatures that are triggered by vitamin D and its derivatives. Studies have also shown that inhibition of vitamin D catabolizing enzyme CYP24A1 (24-hydroxylase) potentiates the efficacy of vitamin D. Therefore, it is important to identify more effective combination agents. Recently, several studies have demonstrated the benefits of using drug-repurposing strategies to develop clinically viable drug combinations. One such combination strategy tested the effect of combining anti-hyperglycemic agent metformin with vitamin D and showed a synergistic effect when tested in preclinical colon and rectum models. There is potential to develop novel vitamin-D based hybrid-molecules for the effective treatment of cancers. Although vitamin D is produced in the body, it is important to deliver vitamin D specifically into or within the vicinity of tumor cells. Hence, strategies addressing vitamin D delivery are highly important and delivery systems including nanoparticles such as liposomes, dendrimers, poly lactic-co-glycolic acid (PLGA)-coated nanoparticles have been experimented with. In particular, PLGA-based nanoparticles have shown promising results in reducing the tumor burden.

This Special Issue aims to collate original research and review articles demonstrating the anti-cancer potential of vitamin D and vitamin D-based therapies. Researchers and clinicians are invited to submit basic, translational, or clinical research articles investigating the epidemiological studies, cellular mechanisms, in vitro and in vivo efficacy assessment, combination strategies that potentiate vitamin D, the pharmacological, pharmacodynamic, pharmacokinetic, and toxicological behavior of vitamin D and vitamin D based therapeutics. Studies on new drug delivery systems in cancer are also welcome. We invite submissions of original research and review articles.

Potential topics include but are not limited to the following:

• Epidemiological studies correlating the serum vitamin D level and cancer incidence
• Vitamin D induced anti-cancer signaling cascades
• Combination studies enhancing the therapeutic efficacy of vitamin D
• Nanotechnology-based approaches selectively delivering vitamin D into tumor cells
• Vitamin D induced microRNAs in cancer
• Vitamin D receptor (VDR) mutations in cancer
• Analogs of vitamin D and their safety and anti-tumor efficacy studies
• Structure-activity relationship studies of vitamin D derivatives
• Pharmacological, pharmacodynamic, and pharmacokinetic assessment of vitamin D and vitamin D based therapeutics
• Vitamin D fortified diets and their impact on cancer incidence
• Vitamin D and its impact on anti-tumor immunity