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US researchers identify pancreatic cancer's “Achilles heel”

4 May 2014

A US research team from Georgetown Lombardi Comprehensive Cancer Center in Washington has published a study showing that inhibiting a single protein completely shuts down growth of pancreatic cancer.

The study reported that although suppressing the protein known as Yap didn’t stop the cancer from developing, it prevented it from progressing any further - effectively stopping it in its tracks.

Lead investigator and assistant professor of oncology, Chunling Yi, said: "We believe this is the true Achilles heel of pancreatic cancer, because knocking out Yap crushes this really aggressive cancer. This appears to be the critical switch that promotes cancer growth and progression."

Published in the journal Science Signaling, the study was conducted on both mice and human pancreatic cancer cells. The mice used in the study had mutations in the same two genes - KRAS and P53 - that are found in a large proportion of patients with pancreatic cancer. Around 95% of patients are found to have a KRAS gene mutation and around 75% have a P53 gene mutation.

Because there has been little success to date in developing drugs to target both KRAS and P53, the aim of this study was to look for alternative potential targets involved in the uncontrolled growth of pancreatic cancer that could be the basis to develop new drugs.

They found that Yap was over-expressed in both the mice and the human samples of pancreatic cancer - and they discovered that the KRAS mutation found in most pancreatic cancers actually activates the Yap protein.

"The KRAS mutation uses Yap to make cancer cells grow, so shutting down Yap defuses the mutated gene's activity," Yi explains.

Yap also shuts down activity of the p53 oncogene, though the link between p53 and Yap is not yet known.

"KRAS and p53 are two of the most mutated genes in human cancers, so our hope is that a drug that inhibits Yap will work in pancreatic cancer patients whho have both mutations,”  Yi says.

She added that because Yap is over-expressed in other cancers, such as lung, liver and stomach tumours, work is already underway to develop drugs that will inhibit activity of the protein. 

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