A vitamin D analog may help weaken one of pancreatic cancer’s key defences, potentially making tumours more vulnerable to chemotherapy and immune attack, according to a small clinical trial.

Researchers from the Salk Institute and Dana-Farber Cancer Institute tested paricalcitol, a vitamin D analog already approved by the US Food and Drug Administration for other medical uses, in patients with previously untreated metastatic pancreatic cancer.

The study, published in Nature Cancer, involved 36 patients who received standard chemotherapy alongside either a placebo, intravenous paricalcitol or oral paricalcitol.

The researchers found that paricalcitol could generally be safely combined with chemotherapy and appeared to alter the environment surrounding pancreatic tumours.

Pancreatic cancer is particularly difficult to treat partly because tumours can develop a dense layer of connective tissue around themselves. This tissue contains fibroblasts, which can help protect tumours from drugs and suppress immune responses.

The researchers found that paricalcitol reduced the activation of these fibroblasts without reducing their overall number. It also increased the presence of T cells inside tumours, suggesting the treatment may make the tumour environment less protective.

The approach builds on earlier research at the Salk Institute led by Ronald Evans, who discovered the vitamin D receptor as part of the nuclear receptor family. Previous laboratory studies found that activating the receptor could regulate fibroblasts and reduce fibrosis and inflammation in tissues.

In pancreatic cancer models, vitamin D analogs were found to reverse the activation of cancer-associated fibroblasts and improve responses to chemotherapy.

The clinical trial provided some encouraging signals, although it was not designed to determine whether paricalcitol improves survival.

Among the 24 patients who received paricalcitol, 10 had a partial response to treatment, compared with one of 12 patients in the placebo group. Five patients receiving paricalcitol remained free of disease progression after one year, while none in the placebo group did.

Researchers also found that patients whose tumours had higher levels of the vitamin D receptor appeared to respond better to treatment and had the longest overall survival.

However, the findings need to be interpreted cautiously because of the trial’s small size and its primary focus on safety rather than treatment effectiveness.

Elevated blood calcium was reported in five of the 12 patients who received oral paricalcitol, but the side effect was managed by reducing the dose.

Researchers said the findings support further trials to determine whether vitamin D analogs can improve the effectiveness of chemotherapy or other cancer treatments.

Future studies will also investigate whether vitamin D receptor levels in tumours can help identify patients most likely to benefit from the treatment.

“This study really takes a novel approach for cracking therapeutic resistance in pancreatic cancer,” said Evans, a study co-author and professor at the Salk Institute.

The researchers said larger clinical trials will be needed before the approach can be considered a new standard treatment for pancreatic cancer.