Pancreatic cancer is so deadly in part because it walls itself off from radiation and chemotherapy. An amped-up version of vitamin D can break down those walls, new research shows.
Pancreatic cancer is arguably the worst cancer diagnosis anyone can receive. It has the highest death rate of any type of cancer at 94 percent. Neither radiation nor chemotherapy is effective against pancreatic tumors.
That makes the discovery of a promising new treatment that’s nearly as simple as a home remedy, described today in the journal Cell, all the more amazing. The treatment is a souped-up version of vitamin D, delivered by injection.
The science of pancreatic cancer lags behind that of other types of cancer, partly because the disease has only become common in recent years.
Looking at how the cancer works at the molecular level, researchers at the Salk Institute near San Diego, California, found that, in an effort to contain the cancer, the pancreas walls it off with dense, inflamed tissue.
“The pancreas is building a safe around the tumor. It’s reasonably successful for doing that for a while, but drugs cannot get to the tumor because it’s being protected by this living safe,” said Ronald Evans, director of the Gene Expression Laboratory at the Salk Institute and the paper’s senior author.
Evans and his colleagues wanted to figure out how to break into the safe. They discovered that the cells that make up the living safe, called stellate cells, had high levels of a particular vitamin D receptor. Introducing the vitamin could return them to their normal, more pliant state. But regular vitamin D supplements weren’t up to the task: It took a powerful synthetic derivative to crack the safe.
Mice with pancreatic tumors that were treated with the modified vitamin D along with anti-cancer drugs lived 50 percent longer than those that got just the drugs.
“It’s one of the reasons that this approach has come a little bit out of left field, because people had tried vitamin D, but they tried regular vitamin D and that simply does not have the power or the impact to get you where you want to go fast enough,” Evans said.
Pancreatic cancer patients often experience vitamin D deficiencies. It’s not clear why, but it appears that the cancer has learned to use the body’s safe-building response against it. A healthy supply of vitamin D may help keep stellate cells in their normal state, which is less beneficial for the cancer.
It may also be that vitamin D deficiency is an early symptom of cancer. Evans and his colleagues found that pancreatic tumors appeared to “grind down” vitamin D because they recognize it as a threat.
But cancer can’t keep up with the new synthetic version of vitamin D for long, giving doctors an opportunity to attack the tumor with drugs or radiation.
The results of the study were so promising that the modified vitamin D is already being given to human patients. University of Pennsylvania researchers began giving the vitamin D to pancreatic cancer patients in February. Because the trial is double blind, there’s no way to know if the approach is working.
Evans credited the group Stand Up to Cancer, which has partnered with his team on the research, for the speed of the transition from the lab to the clinic.
Until recently, scientists thought stellate cells were unique to the liver. Evans and his colleagues also began by researching the liver. But then they found stellate cells in the pancreas and expanded their work. Now, they’re exploring whether stellate cells might be in play when the liver, kidney, or even lungs respond to cancerous tumors.
These cancers also surround themselves with a living tissue “safe.”
“We believe [stellate cells] are more widely found in other organs. If that’s true, then this kind of therapy can expand,” Evans said.