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Malignant tumors are heterogeneous diseases characterized by uncontrolled cell proliferation, invasion, metastasis, and/or recurrence of their malignancies. In particular, cancer stem cells (CSCs) within these tumors might be responsible for the property of invasiveness and/or therapies-resistance. CSCs are a self-renewing, awfully tumorigenic subpopulation of cancer cells, which are notorious for strong chemoresistance and are frequently responsible the aggravated invasion, metastasis, and/or recurrence. Developing targeting therapies against CSCs, therefore, may be deliberated a more encouraging mission for the greater cancer therapy. Innovation for a more potent anti-CSC treatment has been required as soon as possible. Interestingly, vitamin D could modulate the inflammatory condition of the tumor microenvironment (TME) by successfully affecting CSCs, which has an imperative role in determining the malignant phenotype of CSCs. In addition, vitamin D may also contribute to the regulation of the malignant behaviors of CSCs. Consistently, vitamin D could have potential applications for the significant inhibition of several tumor growths within various cancer therapies. The biological significance of vitamin D for CSCs regulation may be involved in the function of APRO family proteins. Therefore, vitamin D could be one of the innovative therapeutic modalities for the development of novel CSCs related tumor therapies.
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