Modified Vitamin D Shows Promise as Treatment for Pancreatic Cancer

Pancreatic cancer is amongst one of the deadliest forms of cancer; it has taken the lives of some of the most well-known figures of recent years like Steve Jobs and Patrick Swayze. As per the National Institutes of Health, every year 46,000 people in the United States are diagnosed with cancer and about 40,000 people succumb to this disease. A new research by the Salk Institute has brought a new ray of hope in the treatment of pancreatic cancer. The researchers at the Institute have found a synthetic derivative of Vitamin D that seems to collapse the barrier of cells that shields pancreatic tumors. As a result of this therapeutic drugs can be much more effectively used to treat the cancer.

Ronald Evans, director of Salk’s Gene Expression Laboratory and senior author of the new paper said, “While the success of this drug in humans with pancreatic cancer is still unclear, the findings in animal studies were strong, raising hope that ongoing clinical trials will give people with this terrible disease hope for a truly new type of therapy.

If successful this new therapy could also prove instrumental in treating other tough-to-treat tumors like lung, liver and kidney cancer. The survival rate for pancreatic cancer is the lowest in the last five years. Evans, holder of Salk’s March of Dimes Chair and a Howard Hughes Medical Institute investigator said that part of the problem is that the science of pancreatic cancer and its renowned resistance to therapy has not been understood. That is why the work that is being carried out in that regard is so important.”

Pancreatic tumor has the ability to communicate with nearby cells, also known as the tumor microenvironment and it is one of the key factors for its growth.  When the tumor cells send out signals, the microenvironment gets inflamed and dense which helps the cancer grow. Not only that, it also blocks the access of immune cells and chemotherapeutic drugs which makes the cancer particularly hard to treat. It was theoretically known that the activation of the microenvironment was reversible, but it was not known what was responsible for the activation in first place, making it hard to turn off, observed postdoctoral research fellow Mara Sherman, first author of the new paper.

The researchers focussed on one component of this shield around the tumor – the pancreatic stellate cells. These cells usually respond to small injuries by switching to an activated state for a brief time and spurs new cell growth. In the state of cancer, the stellate cells near a tumor are constantly turned on. This constant activation of the stellate cells provides the tumor cells with extra growth factors and therefore helps them proliferate. They also form a wall-like barrier because of which chemotherapeutics and other cancer-fighting drugs cannot do its work and treat the cancer cells.

Evans’ group in 2013 discovered that the stellate cells in the liver could be inactivated by a chemically modified form of vitamin D.  They speculated if it could work the same way in pancreas, although it was thought that vitamin D receptor was not typically present in pancreatic tissue. When the activated and inactive stellate cells in the pancreas were examined, the group of researchers found that the activated stellate cells near a tumor had high levels of the vitamin D receptor. When modified vitamin D was added to the activated stellate cells, the cells quickly reverted back to a healthy, inactivated state. They also noticed that the cells stopped the production of signals that spur growth and inflammation.

In previous experiments when normal vitamin D was added in activated stellate cells, it was rapidly broken down. However, the modified version of vitamin D didn't break down and was more stable, resilient and effective in vitro. The effectiveness of the new vitamin D-like compound have been tested in mice and it is found that combining the drug with existing chemotherapeutics can give a 50 percent increase in lifespan compared to chemotherapy alone. The vitamin D doesn't attack the cancer cells; instead it changes the environment for the chemotherapy drugs to work.”

Evans group has teamed up with clinicians at the University of Pennsylvania to launch a clinical trial testing the effectiveness of using the modified vitamin D-like drug in cancer patients before pancreatic surgery.

References

https://www.salk.edu/news/pressrelease_details.php?press_id=2051

https://www.sciencenewsline.com/summary/2014092517310044.html