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Publication Abstract from PubMed

BACKGROUND AND PURPOSE: Castration-resistant prostate cancer (CRPC) is a common male malignancy that requires new therapeutic strategies due to acquired resistance to its first-line treatment, docetaxel. The benefits of vitamin D on prostate cancer (PCa) progression have been previously reported. This study aimed to investigate the effects of vitamin D on chemoresistance in CRPC. EXPERIMENTAL APPROACH: Structure function relationships of potent vitamin D analogues were determined. The combination of the most potent analogue and docetaxel was explored in chemoresistant primary PCa spheroids and in a xenograft mouse model derived from a patient with a chemoresistant CRPC. KEY RESULTS: Here, we show that Xe4MeCF3 is more potent than the natural ligand to induce vitamin D receptor (VDR) transcriptional activities and that it has a larger therapeutic window. Moreover, we demonstrate that VDR agonists restore docetaxel sensitivity in PCa spheroids. Importantly, Xe4MeCF3 reduces tumour growth in a chemoresistant CRPC patient-derived xenograft. In addition, this treatment targets signalling pathways associated with cancer progression in the remaining cells. CONCLUSION AND IMPLICATIONS: Taken together, these results unravel the potency of VDR agonists to overcome chemoresistance in CRPC and open new avenues for the clinical management of PCa.

A vitamin D-based strategy overcomes chemoresistance in prostate cancer.,Len-Tayon K, Beraud C, Fauveau C, Belorusova AY, Chebaro Y, Mourino A, Massfelder T, Chauchereau A, Metzger D, Rochel N, Laverny G Br J Pharmacol. 2024 Jul 9. doi: 10.1111/bph.16492. PMID:38982588^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.