VDR (Vitamin D Receptor)

The results indicate that those variants in the VDR FokI and TaqI genes may increase the predisposition to hepatocellular carcinoma among Egyptians.

No variant correlated with 25(OH)D levels. These findings suggest that FokI, BsmI, and low 25(OH)D independently contribute to BrCa risk in Bangladeshi women.

AITC provides a robust molecular basis for improving MASLD by activating hepatic VDR and driving the downstream HNF-4α/MTTP/ApoB signaling pathway. This pathway reduces hepatic lipid accumulation, promotes FA β-oxidation, and improves insulin resistance, establishing AITC as a promising treatment for MASLD.

This review systematically addresses: (1) the association between VDR expression (assessed by immunohistochemistry) and cancer prognosis; (2) the roles and mechanisms of VDR in cancer; (3) the multi-level regulatory networks governing VDR expression and activity; and (4) the translational implications of VDR in cancer therapy. Elucidating the precise roles and mechanisms of VDR is critical for optimizing cancer treatment strategies and resolving conflicting clinical evidence.

Mechanistically, we show that 1α,25(OH) 2D 3 upregulates the expression of the vitamin D receptor (VDR), promoting transcriptional reprogramming associated with memory-like differentiation and downregulation of exhaustion-related genes, thereby reshaping the functional heterogeneity of CAR-T cells under tumor stimulation. Our study highlights 1α,25(OH) 2D 3 supplementation as a safe and accessible approach to mitigate terminal differentiation and exhaustion of CAR-T cells, offering a promising strategy to enhance the clinical efficacy of CAR-T therapy in patients with R/R DLBCL.

In vivo, triple therapy inhibited tumor growth, reduced peritoneal metastases, and improved survival (~ 85%), with limited systemic toxicity.The combination of GEM, CAL, and HT shows strong synergistic anti-cancer effects both in vitro and in vivo. This triple therapy enhances treatment outcomes in resistant tumors such as PDAC and represents a clinically relevant, low-toxicity approach for multimodal cancer treatment.

Key uncertainties remain, including tissue heterogeneity of VDR expression, optimal dosing windows and target 25(OH)D ranges for cervical endpoints, and safety at higher exposures such as hypercalcemia. This review aims to integrate mechanistic and clinical evidence, define stage-specific roles of the VitD-VDR axis across the CIN-cancer spectrum, and outline practical strategies and research priorities for VitD-based adjunctive interventions in HPV-associated cervical disease.

These findings demonstrate that coclaurine and reticuline exert anti-CRC and pro-apoptotic activities via the VDR, suggesting them as natural therapeutic candidates. The use of in vivo CRC models is needed to validate the anticancer activities of coclaurine and reticuline.

Hydrogen-deuterium exchange mass spectrometry revealed that MeTC7 binding prevents optimal folding of the C-terminal region of VDR and impacts H10, which is part of the dimerization interface. Overall, our findings highlight a new mechanism of action for a VDR antagonist ligand and provide support for the use of the MeTC7 antagonist to inhibit PD-L1 and block tumorigenesis.