New cellular flaw found in some virulent breast cancers

Researchers at Dana-Farber Cancer Institute have identified a molecular interaction that triggers a particularly aggressive form of breast cancer, and suggest that attacking this target with selective drugs might improve treatment.

In the January issue of Cancer Cell, a team led by Qunyan Yu, MD, and Peter Sicinski, MD, PhD, of Dana-Farber report that the interaction of a certain mutated oncogene and the newly described growth control flaw is seen in about 10 percent of breast cancers and the deadliest ones.

The cancer results from a cascade of molecular events. The overproduction of a common protein, cyclin D1, hyperstimulates a growth switch, CDK4 kinase, causing it to unleash a virulent proliferation of cancer cells and creating a tumor with a very poor prognosis.

"The development of cancer drugs like Gleevec and Iressa have shown that it is possible to block the action of kinases," said Sicinski, "so we hope that these findings will stimulate interest in developing drugs to block CDK4 as a targeted approach to treating this very aggressive cancer."

Breast cancers composed of cells that contain both the overactive cyclin D1- CDK4 switch and a mutated cancer-causing gene ErbB-2 (also known as HER2) are extremely difficult to treat. In one recent study, the seven-year survival rate for women with this subgroup of breast cancers was only about 13 percent.

Clinicians have had some recent success in treating breast cancers with a mutated ErbB-2 gene, which are also referred to as being HER2-positive. The targeted therapy Herceptin blocks the mutation, improving the outlook for such patients, though it doesn't work in all cases. Sicinski said that a CDK4 inhibitor might be used in combination with Herceptin to provide further benefit in these patients.

If a drug to block CDK4 proved feasible, Sicinski said, it may be possible to test women's breast tumors for the presence of the overactive kinase, and then treat those

Contact: Bill Schaller
Dana-Farber Cancer Institute

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