Resumen de la ponencia

Dra. A. Dusso

Vitamin D deficiency is strongly associated with increased risk for cancer development and progression. Furthermore, severe vitamin D deficiency concurs with carcinomas of the worst prognosis. Because even the strongest associations do not constitute a proof of causality, the goal of this talk is to present the existing evidence of novel and critical molecular mechanisms underlying the anti-cancer properties of vitamin D that should help prevent/attenuate tumor progression and metastasis. Specifically: a) Inhibition of ADAM17, an enzyme that exacerbates tumor growth, metastasis, immune escape, injury of normal tissue upon radiation and also responsible for the induction of resistance to anti-EGFR therapy; b) Suppression of cathepsin L in BRCA1 deficient tumors thereby stabilizing 53BP1 to compromise proliferation in response to radiation and PARP inhibitors; c) Induction of microRNA145, whose reductions associate with marked increases in ADAM17 expression and also with the release of exosomes propagating exacerbated growth and invasive signals to adjacent normal cells. In turn, the rate of tumoral growth severely compromises intra-tumoral vitamin D metabolism and actions through decreases in tumor levels of the vitamin D receptor (VDR), mandatory for vitamin D anti-tumoral actions, and by increasing the expression of Cyp24A1, the enzyme responsible for the catabolism of active vitamin D metabolites. These are potential mechanisms to aggravate both VDR and vitamin D deficiency in cancer patients. In fact, studies in human endometrial carcinomas have demonstrated that increases in local activation of vitamin D within a tumor contribute to effectively prevent VDR reductions and also the increases in proliferation rates. In addition to these novel anti-tumoral actions, adequate vitamin D supplementation was shown to improve musculoskeletal pain in breast cancer patients treated with aromatase inhibitors and the quality of life in cancer patients undergoing palliative care. In summary, personalized vitamin D supplementation strategies should help improve cancer progression and the general well being of cancer patients.