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Compound enhances cancer-killing properties of agent in trials
Date:6/9/2010

Adding a second agent may make a new, experimental anti-cancer drug effective against a wide range of cancers, researchers at the University of Illinois at Chicago College of Medicine have found.

A man-made compound called ARC was shown by UIC researchers in 2006 to cause tumor cells to die while leaving normal cells unharmed. ARC, an acronym for its long chemical name, resembles one of the chemical building blocks of DNA. Andrei Gartel, associate professor of molecular genetics, and coworkers found it by screening more than 2,000 compounds for their ability to inhibit a key step in the cell cycle.

Now Gartel's laboratory has found that adding ARC may greatly broaden the activity of an anti-cancer agent from Abbott Laboratories that is currently in FDA trials, making it effective in killing a wide range of cancer types.

The results are published online in the journal Molecular Cancer Therapeutics.

In the earlier study, ARC was able to induce apoptosis, or cell suicide, in cancer cells, and only did so to a much lesser extent in normal cells, said Gartel, who is also principal author on the new study.

ARC works mainly by targeting MCL-1, a member of the Bcl-2 family of cellular molecules, which protect cancer cells from the apoptosis induced by anti-cancer drugs. Gartel and his colleagues were interested in whether ARC might be able to improve the activity of Abbott's investigational drug ABT-737, which inhibits several other members of the Bcl-2 family, but not MCL-1.

ABT-737 alone is effective against some small-cell lung cancer cell lines and leukemia cells, but ineffective against other cancer cells, including renal and prostate cancer cell lines.

Gartel and his colleagues knew from other research that because MCL-1 has a protective effect, preventing apoptosis, ABT-737 was not effective in cancer cells with active MCL-1. They decided to see if ARC, which inactivates MCL-1, could work to
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Contact: Jeanne Galatzer-Levy
jgala@uic.edu
312-996-1583
University of Illinois at Chicago
Source:Eurekalert

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