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Modified vitamin D shows promise as treatment for pancreatic cancer

30 September 2014

A synthetic form of vitamin D has been found to collapse the thick fibrous tissue, called stroma, surrounding pancreatic tumours, making the cancer much easier for drugs to reach.

The discovery, published in the journal Cell, was led by a research team from the Salk Institute for Biological Studies in the USA and has already led to human clinical trials.

Ronald Evans, director of Salk's Gene Expression Laboratory and lead author of the 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."

The research team knew that a key factor in the growth of pancreatic tumours is their ability to communicate with nearby cells — called the tumour microenvironment. Tumour cells send out signals that make the microenvironment inflamed and dense. This protective stroma around a tumour not only helps the cancer grow, but blocks the access of immune cells and chemotherapeutic drugs, making the cancer particularly hard to treat.

Evans wanted to figure out how to restore this inflamed microenvironment to its ‘normal’ state and weaken the wall around the tumour. He and his colleagues looked at pancreatic stellate cells, which are usually briefly ‘activated’ to aid new cell growth. Nearby a tumour, however, the stellate cells are hijacked by tumour signals to remain activated.  This provides the tumour cells with extra growth factors and therefore helps them proliferate, and also forms a stroma barrier around the tumour.

In 2013, Evans' group discovered that stellate cells in the liver could be ‘switched off’ by a chemically modified form of vitamin D. They wondered whether the same could hold true in the pancreas.  

When the researchers added modified vitamin D to activated stellate cells, the cells quickly reverted back to a ‘switched off’ state, stopping production of signals that spur growth and inflammation.

When the team repeated the experiment with mice, they found that combining the drug with existing chemotherapeutics gave a 50 per cent increase in lifespan compared to chemotherapy alone.

"It's really remarkable considering that vitamin D itself is not attacking the cancer cells," says Michael Downes, a senior staff scientist at Salk and co-corresponding author of the new work. "It's changing the environment to a more favourable setting needed for the chemotherapy drugs to work."

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

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