Without Kras, Pancreatic Cancer Crashes

Pancreatic cancer survival dependent upon Kras oncogene

(RxWiki News) Pancreatic cancer is one of the most mysterious of all malignancies. The scientific knowledge base of this malignancy has just expanded by volumes thanks to new understanding about a mutant gene that's in the driver's seat.

Researchers have discovered that advanced pancreatic cancer in mice can't survive without a gene called K-ras that's at the heart of how tumors develop and grow.

"Learn about what kind of genetic testing is recommended for your condition."

Investigators at Dana-Farber Cancer Institute suggest that these findings may open new doors for developing targeted therapies to go after this especially lethal malignancy.

The researchers found that advanced pancreatic cancers are what they called "addicted" to the K-ras oncogene.

When the scientists shut down the gene in mice, pancreatic tumors withered rapidly and in some cases disappeared.

"This experiment allowed us to demonstrate that pancreatic cancers in their native setting are dependent on continued oncogenic Kras expression for tumor maintenance," says Alec Kimmelman, MD, PhD, co-corresponding author of the report, along with Ronald DePinho, MD, formerly at Dana-Farber and now President of The University of Texas MD Anderson Cancer Center.

An expert in esophageal cancer, James Farrell, MD,  tells dailyRx, “K-ras is the most commonly mutated abnormal gene in pancreatic cancer. The mutated k-ras gene is felt to be essential for the initiation and propagation of pancreatic cancer."

"However strategies to target therapies towards the mutated k-ras itself have proved very difficult," said Dr. Farrell, who is director of the University of California Los Angeles Medical Center Endoscopic Ultrasound Division of Digestive Diseases.

To find out if advanced pancreatic cancers needed the K-ras oncogene to survive, scientists created a mouse model of the disease in which the gene could be switched on and off with diet changes.

When the oncogene was switched off the tumors in the mice started to shrink in two or three days. After a week, they had shriveled by an average of 50 percent and were shown to be inactive, meaning they were no longer  feeding on glucose, which is essential tumor fuel.

Dr. Farrell explains, "This current research identifies important sugar metabolism pathways which are related to the abnormal k-ras gene and thought to be also central to pancreatic cancer development. This will hopefully allow for the development of new drugs to target these sugar-metabolism pathways and provide novel treatments for pancreatic cancer,” he said.

This research was published in April, 2012 in the journal, Cell.

No financial disclosures or funding information were provided.

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Review Date: 
May 9, 2012