( For nearly a decade scientists have be...)Researchers identify target for cancer drugs

For nearly a decade, scientists have been trying to fully understand a particular communication pathway inside of cells that contributes to many malignant brain and prostate cancers. While scientists have identified elements of this pathway, other key components have remained a mystery. Researchers at Whitehead Institute now have discovered a missing puzzle piece, a finding that may present drug makers with a significant new cancer target.

"We believe that we have identified a component that researchers have been looking for since 1996," says Whitehead Associate Member David Sabatini, who is also an Assistant Professor of Biology at MIT.

At the heart of this new research is a protein called Akt, an important player in the regulation of cell division and survival. Abnormally high activation of Akt has long been implicated in a variety of cancers. If Akt travels to the cell membrane, it is switched on and promotes cell division, often contributing to tumor growth as a result. However, as long as it stays within the cell cytoplasm, it remains relatively inactive. That's because the tumor-suppressor protein PTEN keeps Akt in check by destroying lipids in the cell membrane that normally draw Akt to the surface. In a sense, PTEN keeps a leash on Akt and thus suppresses cell division.

But when PTEN is mutated and unable to function, Akt breaks free. It makes its way to the cell membrane where other proteins activate it, thereby enabling Akt to contribute to tumor growth. "When a cell loses PTEN through, say, a mutation, Akt goes gangbusters," says Sabatini.

The exact means by which Akt switches on when it reaches the cell membrane has only been partially understood. As a result, researchers have lacked a clear idea about how to prevent the process. However, in the February 18 issue of the journal Science, researchers from the Sabatini lab report on discovering an important missing piece of the activation process.

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Source:Whitehead Institute for Biomedical Research

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