Synthetic Vitamin D the Missing Link in Pancreatic Cancer Treatment?

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Salk_pancreatic cancer PUBResearchers from the Salk Institute, La Jolla, Calif, have found that a manmade derivative of vitamin D caved-in the seemingly impervious wall of cells barricading pancreatic tumors, cleaving a gap in which to pump cancer-fighting drugs.

The findings, from animal studies, have led to human trials.

The dismal five-year survival rate for this type of cancer—lowest among all cancers—may be linked to our inability to find its Kryptonite-like vulnerability. In the United States, some 46,000 people are given this diagnosis each year, and 40,000 people die from the disease.

The cells surrounding a pancreatic tumor provide fertile ground for it to spread, and also form a blockade that immune cells and chemotherapy drugs cannot penetrate. The researchers sought a way.

They concentrated their efforts on pancreatic stellate cells, which generally react to slight injuries by temporarily converting to an activated state, triggering new cells to grow. When a person has cancer, the stellate cells around a tumor are continually turned on. Viscous cycle: cells multiply, wall strengthens. Having previously found that stellate cells in the liver could be thwarted by a synthetic form of vitamin D, the team questioned if this was also true for the pancreas—even though it was not evident there was a vitamin D receptor in pancreatic tissue. Good news . . . activated stellate cells neighboring a pancreatic tumor had high levels of the vitamin D receptor, and better news, when they added the synthetic vitamin D to these activated cells the cells switched back to an inactive state, extinguishing signals that promoted growth and inflammation. The novelty of the researchers’ approach may have been in using modified vitamin D.

When the vitamin D-like drug was mixed with chemotherapy drugs in a study with mice, the mice had a 50 percent increase in lifespan versus chemotherapy by itself.

For some reason I’m reminded of the slogan repeated in many a commercial break years ago by the BASF chemical company, “We don’t make a lot of the products you buy. We make a lot of the products you buy, better.” In this instance, the researchers note that the vitamin D is not bombarding the cancer cells, it is modifying the environment into one that is more conducive for chemotherapy drugs to work. This approach paves the way for transporting more drugs to the tumor and refreshing the tissue with normal stellate cells.

Image: In the pancreatic tumor microenvironment, noncancerous stromal cells (blue) impede the delivery and efficacy of chemotherapy. [Photo credit: Salk Institute for Biological Studies]

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