Vitamin D receptor in tumors: A review of biological mechanisms, therapeutic potentials, and prognostic values.

The vitamin D receptor (VDR) is a key regulator of cellular growth and differentiation, and accumulating evidence links vitamin D signaling to tumor biology.

However, the specific contributions of VDR across diverse cancers remain incompletely understood. This narrative review synthesizes current knowledge on the dualistic mechanisms of VDR in oncogenesis, integrating preclinical, translational, and early-phase clinical evidence across solid tumors and hematologic malignancies. In many contexts, ligand-activated VDR predominantly performs tumor-suppressive functions by inducing cell cycle arrest, promoting apoptosis, inhibiting metastasis, enhancing DNA repair capacity, and modulating epigenetic landscapes. Paradoxically, in specific tumor contexts, VDR may foster pro-oncogenic phenotypes through the establishment of immunosuppressive microenvironments or the perpetuation of oxidative stress.

Preclinical evidence indicates that VDR activation may enhance the sensitivity of tumor cells to radiotherapy and chemotherapy. Translational and early-phase clinical evidence, predominantly from breast and colorectal cancer, identifies VDR as a promising therapeutic target and prognostic biomarker, although these findings remain hypothesis‑generating and require further validation. A deeper understanding of VDR biology is critical for clarifying its tumor-specific roles. Defining these mechanisms will not only improve prognostic accuracy but also enable the development of targeted interventions, ultimately advancing the use of VDR-based strategies in precision oncology.