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Molecular Flaw Detected in Aggressive Breast Cancers

A molecular flaw that lets loose a particularly aggressive from of breast cancer has been discovered by the researchers at Dana-Farber Cancer Institute. They suggest that targeting this flaw with selective drugs could help victims of this type of breast cancer. //

The team of researchers led by Qunyan Yu, MD, and Peter Sicinski, MD, PhD, of Dana-Farber details their finding in the January issue of Cancer Cell. They report that this particular growth flaw interacts with a mutated oncogene and triggers a potentially fatal type of breast cancer. This flaw is seen in 10 percent of all breast cancers. This flaw causes the overproduction of a protein called cyclin D1, which triggers CDK4 kinase. This is a "growth switch", which unleashes a virulent proliferation of cancer cells. "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, which have overactive cyclin D1- CDK4 as well as the mutated cancer-causing gene ErbB-2 (also known as HER-2) are next to impossible to detect. One study had found the seven-year survival rate of women affected by this type of cancer to be just 13 percent. In recent times, Herceptin has targeted the mutation and blocked it, thereby improving the prognosis for Her-2 positive women. Sicinski pointed out that a CDK4 inhibitor could be combined with Herceptin to benefit patients. "We are going to see in the next five years a movement away from treating all tumors with the same drugs, and instead match specific drugs to tumors based on their molecular characteristics," said Sicinski, an associate professor of pathology at Harvard Medical School.

Co-authors of the paper are from Linkoping University, Linkoping, Sweden; Biogen Idec, Cambridge, Mass.; and Northwestern University, Ch
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