Researchers from the Fred Hutchinson Cancer Research Center in Seattle are engaging in a new strategy to identify promising new anticancer compounds-and eventually spur the development of highly selective new drugs against the disease.

They contend that their approach makes it possible to broadly screen a large number of compounds for those that can selectively kill cells with cancer-causing genetic mutations. Their findings appeared in the Journal of the National Cancer Institute.

Heather Dunstan, Ph.D., John Lamb, Ph.D, and their colleagues at Hutchinson wrote that their new "cell-based" approach can screen an entire library of compounds to identify those that are toxic against cells with known genetic mutations. These compounds can then be isolated for further testing, possibly leading to the development of a new anti-cancer therapies.

Using their three-stage, cell-based approach on compounds selective for yeast cells, Dunstan's team identified 39 new compounds 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 Institute's repository for compounds with defective DNA repair enzymes.

In an accompanying editorial, Dr. Frank Balis of the National Cancer Institute said that this new approach is adaptable to the so-called "high-throughput screening method," which allows researchers to screen large libraries of compounds and quickly identify those that show anti-cancer promise.

He said that the target-specific cell-based screening approach reported by Dunstan and her colleagues "represents a dramatic shift in the drug discovery process that is likely to have an impact not only on the pharmacologic properties of new anticancer agents reaching the clinic, but also on our approach to clinical drug development and the treatment of cancer."

SOURCE:
Journal of the National Cancer Institute, January 16, 2002; 94(2):78-79, 88-94