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New method for anticancer drug discovery developed

Researchers have developed a new strategy to identify potential anticancer compounds. The system makes it possible to screen for compounds that can selectively kill cells that carry specific mutations often found in cancer cells, such as those in cell cycle checkpoint proteins. The findings appear in the Jan. 16 issue of the Journal of the National Cancer Institute.

Current approaches to anticancer drug discovery are target-based, where researchers design compounds that specifically interact with proteins that are involved in cancer. Although this approach has led to the discovery of compounds such as angiogenesis inhibitors, it is limited by the lack of knowledge about the specificity of the compounds, say Heather M. Dunstan, Ph.D., John R. Lamb, Ph.D., and colleagues at the Fred Hutchinson Cancer Research Center, Seattle.

The new cell-based approach, rather, is based on screening compounds against cells with specific genetic mutations. Using this approach, researchers can screen an entire library of compounds against many cells that each contain a different genetic mutation. Compounds that are specifically toxic against cells with defined mutations would undergo further testing.

The approach is adaptable to the so-called high-throughput screening method, which allows researchers to screen large libraries of compounds and quickly identify lead compounds, says Frank M. Balis, M.D., National Cancer Institute, in an editorial.

Using their three-stage, cell-based approach, the authors identified 39 new compounds selective for yeast cells that have a faulty DNA repair enzyme called rad50. The authors found these compounds by screening more than 85,000 compounds from the National Cancer Institutes repository for compounds that are selective against yeast cells with defective DNA repair enzymes.

Although exactly how the compounds act is yet to be determined, the authors maintain that it is better to have compounds with a k
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Contact: Linda Wang
jncinews@oup-usa.org
301-594-2927
Journal of the National Cancer Institute
15-Jan-2002


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