Researchers Explore Vitamin D Drug to Break Pancreatic Cancer's Natural Defences

A vitamin D analog may help weaken the protective environment surrounding pancreatic tumours and improve responses to chemotherapy, according to an early clinical trial published in Nature Cancer.

The study included 36 people with previously untreated metastatic pancreatic cancer. Participants received standard chemotherapy with either a placebo or the vitamin D analog paricalcitol, given orally or intravenously. The main aim was to assess safety rather than treatment effectiveness.

Overall, paricalcitol could be combined safely with chemotherapy. However, five of the 12 patients receiving the oral form developed high blood calcium levels. The side effect was managed by reducing the dose.

Researchers also examined tumour biopsies before treatment and after four to six weeks. Paricalcitol reduced activation of cancer-associated fibroblasts, connective tissue cells that contribute to the dense, fibrotic environment surrounding pancreatic tumours. The treatment also increased infiltration of T cells, immune cells involved in attacking abnormal cells.

These findings support earlier laboratory research suggesting that activating the vitamin D receptor can remodel the tumour microenvironment rather than directly killing cancer cells.

Although the trial was not designed to establish treatment effectiveness, researchers observed encouraging signals. Among 24 patients receiving paricalcitol, 10 had a partial response, compared with one of 12 patients receiving placebo. Five patients in the paricalcitol groups remained free from disease progression at one year, compared with none in the placebo group.

Patients whose tumours had higher levels of the vitamin D receptor appeared to respond better and had the longest overall survival.

However, these findings should be interpreted cautiously.

Larger randomised trials are needed to determine whether vitamin D receptor activation can safely improve pancreatic cancer treatment and whether tumour receptor levels can identify patients most likely to benefit.

REFERENCE: Kimberly J. Perez, et al.; Gemcitabine and nab-paclitaxel with or without the VDR agonist paricalcitol for metastatic pancreatic cancer: a randomized, multiarm, run-in phase trial. Nature Cancer, 2026; 7 (6): 928 DOI: 10.1038/s43018-026-01165-8