Screening technique streamlines search for antica...( e compounds based on their effectivenes...)

"Using this system, we searched for compounds that become active only in the presence of commonly mutated genes," says Stockwell. "We've identified several compounds, including one previously unknown compound, that had exactly the effect we were looking for."

Mass screening like this--what scientists call high-throughput testing--represents a new and emerging paradigm in drug discovery. "The old method to find drug candidates was to take tumor cells from a human tumor, and find things that killed them, without really understanding how they would ultimately affect other cells in the body," Stockwell explains. "Drug candidates identified by this method often turned out to be completely toxic to healthy cells and thus, not usable as a therapy."

In addition to investigating its therapeutic implications, Stockwell and his colleagues are using this screening technique to study the cell signaling pathways driving tumor growth.

Erastin

Of the compounds Stockwell's team identified, four are currently used in clinical practice to treat tumors. A better understanding of how these drugs work may offer vital insight into which drugs are more likely to be effective against a particular type of cancer. "We discovered that these anticancer drugs are particularly effective in tumor cells with specific genetic changes, suggesting a strategy by which we can tailor the use of these drugs to fit a patient's unique tumor type," says Stockwell.

One of the compounds found to be more potent in the presence of the cancer-linked genetic aberrations has never been studied nor its potential as an anticancer drug explored. Stockwell's group currently is conducting follow-up studies to determine how this unique compound, which they named er
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Contact: Melissa Withers
withers@wi.mit.edu
617-258-7403
Whitehead Institute for Biomedical Research
26-Mar-2003