Scientists working on ways to treat pancreatic cancer — one of the hardest cancers to manage — have developed a drug from a modified form of vitamin D, which they found in a recent study to dismantle the protective shields surrounding tumors.

Each year, roughly 46,000 people are diagnosed with pancreatic cancer. Due to a lack of effective screening and treatment options, all but 6,000 of those people will go on to die. The five year-survival rate is the lowest of all cancers, according to the National Institutes of Health, prompting researchers to investigate how, exactly, the disease avoids eradication.

"Part of the problem is that the science of pancreatic cancer and its renowned resistance to therapy has not been understood and that's why the work that we're doing is so important,” said Ronald Evans, director of Salk Institute’s Gene Expression Laboratory and senior author of the new report, in a statement.

Science knows this much: Pancreatic cancer cells rely on the communication with neighboring cells to coordinate their growth. This cooperative is known as the “tumor microenvironment,” and it sends out signals to each tumor to produce a dense and inflamed barrier — similar to a shield — that accommodates growth and blocks immune cells and chemotherapeutic drugs from attacking.

Prior research has shown these barriers aren’t permanent; in theory, they can be forcibly reversed. But no one had discovered the logistics of actually doing it. So Evans and a team of colleagues got to work applying their existing research base — studies into vitamin D’s interaction in the liver — to matters of pancreatic cancer treatment.

The main driver of the investigation was a group of cells known as stellate cells. They comprise one component of the wall that makes up cancer cells’ defenses. Usually they switch between activation states, but in the presence of cancer they stay activated. So, the cells provide the tumor with extra growth factor, which lets the cancer proliferate. Liver tests showed a modified form of vitamin D helped deactivate stellate cells. The only problem is, pancreatic tissue doesn’t contain vitamin D receptors.

At least, that’s what Evans and his team thought. When they looked at the stellate cells near a tumor, they saw clusters of vitamin D receptors. And when they introduced the same modified vitamin D drug, the signals quieted and tumor growth ceased. "This was a big surprise because vitamin D has been tried multiple times as a therapy for pancreatic cancer and never worked," Evans said.

The real magic came in the results of their follow-up tests on mice. With the vitamin D drug, cancerous mice lived 50 percent longer with chemotherapy than they did with just chemotherapy alone. "It's really remarkable considering that vitamin D itself is not attacking the cancer cells," commented Michael Downes, a senior staff scientist at Salk and a co-author of the paper. Instead, the added vitamin D supply creates an environment tilted in chemotherapy’s favor.

Moving forward, the team hopes to bring the trials to the clinical level. In the meantime, Evans advises people to monitor their vitamin D levels, as a deficiency has been linked to pancreatic cancer. Healthy levels may stimulate proper signaling of the stellate cells, minimizing the chance of tumor growth.

“Previous trials with vitamin D failed because they didn't understand the need for a special form of vitamin D and that for pancreatic cancer it must be used in combination with chemotoxic drugs," Evans said. "So, by re-thinking the problem, [we] have been able to open up a new route to the treatment of pancreatic cancer and, looking forward, hopefully other diseases as well."

Source: Sherman M, Yu T, Engle D, et al. Vitamin D Receptor-Mediated Stromal Reprogramming Suppresses Pancreatitis and Enhances Pancreatic Cancer Therapy. Cell. 2014.