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Mutant Kras drives pancreatic cancer maintenance via metabolic pathways
Date:4/26/2012

HOUSTON - A genetic mutation that drives the initiation of pancreatic cancer also manipulates metabolic pathways to support tumor growth and progression, scientists report in the journal Cell.

This newly discovered role for the Kras oncogene opens up a new category of potential targets for thwarting the influential mutation, which has proved difficult to attack directly, said study co-lead author Haoqiang Ying, Ph.D., instructor in The University of Texas MD Anderson Cancer Center Department of Genomic Medicine.

Pancreatic ductal adenocarcinoma has a five-year survival rate of about 5 percent. The National Cancer Institute estimates 43,920 new cases will be diagnosed in 2012 and 37,390 patients will die of the disease.

"Our research provides an additional metabolism angle to the search for therapeutic targets," Ying said. "The highly coordinated regulation of anabolic glucose metabolism by the Kras oncogene also indicates the need to develop combination strategies to target those pathways as well as other functional components of Kras signaling."

The Kras gene produces a protein that's influential in normal cell signaling. Mutated versions of Kras get stuck in a state of permanent activation and are so tightly bound to the enzyme GTP that small-molecule inhibitors have so far been unable to successfully target it, Ying said.

Cancer initiator also fuels growth and progression

"Activating mutations in the Kras oncogene are nearly universal in pancreatic cancers and have been shown to be important in the initiation of these cancers," said study senior author Ronald DePinho, M.D., president of MD Anderson. "The role of this critical gene in the maintenance of these tumors in an in vivo setting had not been explored."

To address this question, DePinho's team at Harvard Medical School and Dana-Farber Cancer Institute, where this research originated, developed an inducible Kras transgene (iKr
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Contact: Scott Merville
smerville@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert

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