Increasing interest in studying the role of
vitamin D in
cancer has been provided by the scientific literature during the last years, although mixed results have been reported.
Vitamin D deficiency has been largely associated with various types of solid and non-solid human
cancers, and the almost ubiquitous expression of
vitamin D receptor (VDR) has always led to suppose a crucial role of
vitamin D in
cancer. However, the association between
vitamin D levels and the risk of solid
cancers, such as colorectal, prostate and
breast cancer, shows several conflicting results that raise questions about the use of
vitamin D supplements in
cancer patients. Moreover, studies on
vitamin D supplementation do not always show improvements in
tumor progression and mortality risk, particularly for prostate and
breast cancer. Conversely, several molecular studies are in agreement about the role of
vitamin D in inhibiting
tumor cell proliferation, growth and invasiveness, cell cycle arrest and inflammatory signaling, through which
vitamin D may also regulate cancer microenvironment through the activation of different molecular pathways. More recently, a role in the regulation of cancer stem cells proliferation and short non-coding
microRNA (
miRNAs) expression has emerged, conferring to
vitamin D a more crucial role in
cancer development and progression. Interestingly, it has been shown that
vitamin D is able not only to potentiate the effects of traditional
cancer therapy but can even contribute to overcome the molecular mechanisms of drug resistance-often triggering
tumor-spreading. At this regard,
vitamin D can act at various levels through the regulation of growth of cancer stem cells and the epithelial-mesenchymal transition (EMT), as well as through the modulation of
miRNA gene expression. The current review reconsiders epidemiological and molecular literature concerning the role of
vitamin D in
cancer risk and
tumor development and progression, as well as the action of
vitamin D supplementation in potentiating the effects of
drug therapy and overcoming the mechanisms of resistance often triggered during
cancer therapies, by critically addressing strengths and weaknesses of available data from 2010 to 2020.