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US research uncovers a potential new drug target

12 June 2012

Researchers have discovered how some types of pancreatic cancer alter the body’s immune system to avoid being destroyed by specialised immune cells. This adaptation allows the cancer to grow unhindered.

“It is extremely important that we learn how the advancement of pancreatic cancer is being regulated in an effort to interrupt the progression of the disease,” said the study’s leader Dr Dafna Bar-Sagi, chief scientific officer at New York University (NYU) School of Medicine.

The researchers from the NYU School of Medicine found that a mutation in a known pancreatic cancer gene - called KRAS - which is present in 95 per cent of all pancreatic cancers, causes the production of a protein called GM-CSF.

In research published in the journal Cancer Cell, the group showed that the GM-CSF protein produced by the tumour causes a build-up of cells that suppress the immune system’s reaction to growing tumour.

This build-up results in the failure of the body to produce the cells–CD8+ T-cells - that normally kill tumours.  This results in pancreatic cancer cells escaping the body’s immune system, leaving them free to grow and divide.

The US team artificially stopped the tumour cells producing the GM-CSF protein and discovered that tumour growth was inhibited because CD8+ T-cells, the body’s natural defence mechanisms, were killing the tumour cells. 

The team found that GM-CSF protein was made in both mouse models of pancreatic cancer and the early stages of human pancreatic cancer that had the mutation in the KRAS gene.

Dr Bar-Sagi said, “Our findings should be applicable to a significant proportion of human pancreatic cancer cases, as the vast majority of human pancreatic cancer samples that we tested express the GM-CSF protein prominently.”

The researchers hope their findings will open new doors in the search for better treatments for pancreatic cancer; perhaps eventually leading to new drug therapies that block the production or function of GM-CSF protein.

“From a research standpoint, the contribution of KRAS mutation to the production of GM-CSF is a very exciting find, as it may have important implications for the therapeutic management of other cancers, as well,” says Dr Bar-Sagi.

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