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Small molecules inhibit growth of human tumor cells
Date:4/13/2011

tances, the inhibitors stopped the proliferation of cancerous cells in the laboratory dish or in the mouse.

"To date, no therapies for the control of Wnt-driven tumors have been available for colon cancer, lung cancer, leukemia, and other forms of the disease caused by mutations in the Wnt pathway," said Robert A. Nagourney, MD, of Rational Therapeutics in Long Beach, California, who is one of the study's authors. "The findings in our human tissue model give us real hope that these compounds will have important implications in future clinical therapy and the development of an effective Wnt inhibitor."

The Wnt pathway is complex and only partially understood. Wnt genes bind to receptors on the surface of cells, provoking a reaction (or a "signaling cascade") within the cell that ultimately allows various "downstream effector proteins" to go into action. One of these proteins, called β catenin, moves into the nucleus and oversees the activation of genes often associated with cell proliferation and other processes.

In the study, the researchers used an innovative, integrated screening platform combining RNA interference (RNAi) -technology and high-throughput chemical genetic screening to examine the potency of 14,977 compounds on the activity of the Wnt pathway. This targeted screening methodology helped identify the three promising novel inhibitors capable of blocking Wnt target genes in various mammalian cancer cell lines including human colon and breast cancer cells. Foster C. Gonsalves, PhD, first author of the study and post-doctoral fellow in Dr. DasGupta's lab, helped develop this technique.

"While more exploratory research of these promising compounds is needed, these small molecules identified in the RNAi screens can serve as prototypes for the development of future antitumor drugs targeting the Wnt signaling pathway in different Wnt-associated cancers," says Dr. DasGupta. "Similar RNAi-based integrated screening technol
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Contact: Lauren Woods
lauren.woods@nyumc.org
212-404-3753
NYU Langone Medical Center / New York University School of Medicine
Source:Eurekalert  

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