Research Uncovers a Potential Weak Link in the Kras Chain

Kras, an influential gene that serves as an on-off switch for other genes, is mutated in 80 to 95% of cases of pancreatic cancer.

"It's also the most frequent mutation found among all cancers," says Paul Chiao, Ph.D., professor in MD Anderson's Department of Molecular and Cellular Oncology.

Attempts to target Kras have been disappointing so far. Chiao and colleagues have discovered a molecular chain of events that exposes new potential weak spots.

A paper in the January edition of the journal Cancer Cell spells out what Chiao describes as a "vicious cycle" -- a self-perpetuating loop of molecular activity that fuels pancreatic cancer by promoting inflammation, development of new blood vessels and blocking programmed cell death.

Basically, mutated Kras triggers a cascade of events that includes inducement of Interleukin-1alpha, which in turn fires up NF-ï_B, a protein complex that controls activation of genes. NF-ï_B induces a number of inflammation-promoting genes, including IL-1alpha, which in turn cycles back to activate NF-ï_B.

Interleukin-1alpha is an interesting potential target for developing a drug to block this process, Chiao notes.

Additional information

MD Anderson news release

Cancer Cell paper. (paywall alert)