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

se method of action has been a mystery, and that knowledge can lead scientists to other, similarly-acting drug candidates.

The gene signatures are captured by devices called microarrays, or "gene chips," that take a snapshot of the tens of thousands of genes at the heart of every cell. The Connectivity Map system is based on the difference in gene activity patterns -- which genes are active, which are inactive -- in a disease cell compared with a normal cell, or a cell before it has been treated with a drug and after the drug has been administered. Usually there is a group of 100 or more genes whose activity differs between one state and the other: That set of genes makes up the signature.

The publications describe how the Connectivity Map, which in its initial edition contained links to 164 different drugs and other chemical compounds, was used to obtain information on treatments for obesity, Alzheimer's disease, and cancer, and to suggest new therapies for drug-resistant leukemia and advanced prostate cancer.

Scott Armstrong, MD, PhD, a pediatric oncologist at Dana-Farber and Children's Hospital Boston, is senior author on a paper in Cancer Cell that describes how the method successfully identified a drug that can overcome therapy-resistant cases of acute lymphoblastic leukemia (ALL) in children. So-called "glucocorticoid" drugs like prednisone are very effective in many cases of ALL, but in some patients the cancer cells are resistant to the drugs, which often can lead to fatal results.

"We took cells from ALL patients that were either resistant or sensitive to glucocorticoids and put them through the Connectivity Map database, and it predicted that one of the best drugs would be rapamycin," said Armstrong, who is also an assistant professor of pediatrics at Harvard Medical School. "Then we tested rapamycin to see if it made the ALL cells more sensitive to glucocorticoids, and in some cell lines it appears that it does," he sa
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Source:Dana-Farber Cancer Institute


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