Discoveries

A small clinical trial led by the Dana-Farber Cancer Institute put a Salk Institute idea to the test in patients: that activating the vitamin D receptor can help reshape the protective environment surrounding pancreatic tumors in ways that could make the notoriously difficult-to-treat cancer more vulnerable to therapeutic treatments.

In the study co-authored by Ronald Evans, PhD, patients with previously untreated metastatic pancreatic cancer received standard chemotherapy with or without paricalcitol—a vitamin D analog that is already FDA-approved for other uses. In patients who received paricalcitol orally or intravenously, the combination was found to be safe and to reduce activation of fibroblasts in the tumor microenvironment, validating Salk’s preclinical findings. The trial was not intended to measure how well the approach works in treating pancreatic cancer, yet the researchers noted improved chemotherapy responses and increased progression-free survival at one year among patients who received paricalcitol plus chemotherapy. In addition, they found that patients with high vitamin D receptor expression and who received paricalcitol had the longest overall survival rate.

“This study really takes a novel approach for cracking therapeutic resistance in pancreatic cancer. By using vitamin D analogs to engage the body’s own natural system for dampening fibrotic and inflammatory responses, we can enable other therapies to do their job.”

Ronald Evans

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