Could Vitamin D Help Treat Pancreatic Cancer? New Trial Offers Encouraging Clues

A small clinical trial has tested a new way to attack pancreatic cancer, one that grew out of laboratory discoveries at the Salk Institute. Led by researchers at Dana Farber Cancer Institute, the study explored whether activating the vitamin D receptor can change the protective environment around pancreatic tumors. If it works, this notoriously hard-to-treat cancer could become more vulnerable to therapies that are already available.

What the trial tested

Published in Nature Cancer, the study enrolled patients with metastatic pancreatic cancer who had not yet received treatment. Some patients received standard chemotherapy alone, while others received chemotherapy plus paricalcitol, a vitamin D analog the FDA has already approved for other medical uses.

Investigators found that the combination was generally safe, regardless of whether paricalcitol was taken by mouth or given intravenously. In patients, the drug also lowered the activation of fibroblasts within the tumor microenvironment, which backed up what Salk scientists had previously seen in the lab.

Encouraging signals, with caveats

The trial was not built to show whether the approach improves pancreatic cancer outcomes, so its results should be read as preliminary. Still, the researchers noted several promising patterns. Patients on paricalcitol plus chemotherapy responded to treatment more often and were more likely to be free of disease progression a year in. The longest overall survival turned up in patients who received paricalcitol and whose tumors carried high levels of the vitamin D receptor.

“This study really takes a novel approach for cracking therapeutic resistance in pancreatic cancer,” study co-author Ronald Evans, PhD, professor and the March of Dimes Chair in Molecular and Developmental Biology at Salk told Science Daily. “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.”

From the lab bench to the clinic

Evans is credited with discovering the nuclear receptor superfamily, a large class of molecules that includes the vitamin D receptor. These receptors sense hormones, vitamins, and lipids, then change how cells behave by turning genes “on” and “off.” The class is already a proven drug target, with roughly 13% of FDA approved drugs acting on nuclear receptors.

In preclinical models, Evans and his colleagues previously found that the vitamin D receptor helps govern fibroblasts in the liver and pancreas. These connective tissue cells can help build the dense, protective structure that shields pancreatic tumors and certain other cancers. The team detected especially high receptor levels in rare fibroblast populations residing within tissues, and the receptor appeared to be important for keeping healthy tissue stable.

The Salk group went on to show that synthetic vitamin D compounds, paricalcitol among them, could prevent liver fibrosis and pancreatitis in experimental models. These compounds are engineered to withstand the natural process that ordinarily breaks vitamin D down, which helps them stay active longer.