Researchers at the Dana-Farber Cancer Institute have shown that advanced pancreatic cancers in mice cannot survive without continued expression of a mutant oncogene that "rewires" key metabolic pathways to fuel the cancer cells. The findings, published in the April 27, 2012 issue of Cell, suggest that some of these altered metabolic pathways might be potential targets for future drugs to treat the deadly cancer. The investigators report that when they experimentally shut down the expression of the Kras oncogene in mice, the pancreatic tumors rapidly shrank, and, in some cases, left no visible signs of cancer. This outcome, they said, provides evidence that advanced pancreatic cancers are "addicted" to the Kras oncogene for their continued growth. "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, M.D., Ph.D., co-corresponding author of the report along with Ronald DePinho, M.D., formerly at Dana-Farber and now at M.D. Anderson Cancer Center in Houston. Dr. Kimmelman said they also discovered that oncogenic Kras "basically reprograms the glucose metabolism of the cell by regulating the expression of key metabolic enzymes, some of which might provide novel therapeutic targets." If that is the case, then attacking these pathways might be more feasible than attempting to block KRAS directly, since KRAS has proven frustratingly difficult to hit with designer drugs. It is estimated that pancreatic ductal adenocarcinoma will be diagnosed in more than 43,000 people in the United States in 2012, according to the American Cancer Society, and more than 37,300 will die from the disease, which has a 5-year survival rate of only 5 percent.
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