Halting Pancreatic Cancer Development

Much of the cancer research community is focused on a search for specific proteins that will produce beneficial effects if levels are augmented or restricted. Here is an example of the sort of work presently taking place:

A research team [reports] that inhibiting a single protein completely shuts down growth of pancreatic cancer, a highly lethal disease with no effective therapy. Their [study] demonstrates in animal models and in human cancer cells that while suppressing Yes-associated protein (Yes) did not prevent pancreatic cancer from first developing, it stopped any further growth. "We believe this is the true Achilles heel of pancreatic cancer, because knocking out Yes crushes this really aggressive cancer. This appears to be the critical switch that promotes cancer growth and progression."

The study was conducted in mouse models of pancreatic ductal adenocarcinoma (PDAC), which accounts for all but five percent of human pancreatic cancers. These mice have a mutation in the KRAS gene, as well as a mutation in their p53 gene. "More than 95 percent of pancreatic cancer patients have a KRAS mutation and about 75 percent have a mutation in p53, so these mice provide a natural model of the human disease."

Because it has been very difficult to devise drugs that target either KRAS or p53, in this study the researchers looked for other potential druggable targets involved in uncontrolled growth of pancreatic cancer. They found that Yes was over-expressed in both mouse models and human samples of PDAC, and they discovered that the KRAS mutation found in most pancreatic cancer activates Yes.

Because Yes is over-expressed in other cancers, such as lung, liver and stomach tumors, researchers are already working on small molecule drugs that will inhibit activity of the protein and its partnering molecules. "KRAS and p53 are two of the most mutated genes in human cancers, so our hope is that a drug that inhibits Yes will work in pancreatic cancer patients - who have both mutations - and in other cancers with one or both mutations."

Link: http://www.eurekalert.org/pub_releases/2014-05/gumc-ho042914.php


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