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Scientists use gene signatures to match cancer and other diseases with potentially effective drugs

In one of the most ambitious spinoffs of the human genome project, researchers at Dana-Farber Cancer Institute, Children's Hospital Boston, the Broad Institute of Harvard and MIT, and other collaborating centers have unveiled a new, systematic approach to drug discovery that matches diseases with potential treatments using a universal language based on cells' distinctive gene activity profiles, or "signatures."

A set of three articles being published in the September 29 issue of Science and in the September 28 advance online edition of Cancer Cell unveils the first steps toward what researchers have dubbed a "Human Connectivity Map."

"The Human Connectivity Map works much like a Google search to discover connections among drugs and diseases," explained Todd Golub, MD, who is an investigator at Dana-Farber, the head of the Cancer Program of the Broad Institute, an associate professor of pediatrics at Harvard Medical School, and a Howard Hughes Medical Institute Investigator. He is a senior author on two of the papers.

The paper in Science describes the concepts underlying the gene signature catalogue and gives an overview of its initial testing. "This should be particularly useful for pharmaceutical companies, so that academic scientists and companies alike can compare the signatures of diseases and compounds to signatures in the Connectivity Map database, and, from that, generate hypotheses," Golub said.

The strategy allows scientists to capture distinctive gene signatures of cancer and other disease cells and compare them with signatures of cells that have been treated with a large number of drugs, both old and new. The more closely the disease signature resembles the signature of a reference cell that has been treated by a particular drug, the greater the odds that the drug will be an effective treatment for that disease.

Conversely, the system can reveal the molecular mechanism of a treatment that is effective but who
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Source:Dana-Farber Cancer Institute


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