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Combination targets: some drugs may work best when they work together
Date:10/24/2007

nter. To understand the connections between these pathways we have taken a systems biology approach, one that may uncover new anti-cancer drug targets on different levels within connecting pathways.

As part of a multi-institutional research effort funded by the National Cancer Institutes Integrative Cancer Biology Program, Dr. Korn and his colleagues at UCSF, Lawrence Berkeley National Laboratories and The University of Texas M. D. Anderson Cancer Center are creating computer models informed by their systemic approach that will enable them to identify important proteins within the signaling networks. There so many different components involved, that modeling these pathways is as complicated as creating computer models that accurately predict the weather, Dr. Korn said.

The MEK protein is an enzyme involved in the well-studied RAS pathway, which plays a central role in promoting cell growth and multiplication. When not functioning properly, this pathway has been implicated in a number of cancers, Dr. Korn says, including breast cancer. When the researchers treated breast cancer cells with molecules designed to bind to and inhibit MEK, named U0126 and CII040, they observed that instead of dying, the cells simply froze at a single point in their life cycle.

While U0126 and CII040 prevented breast cancer cells from growing, they did not kill the cells implying that some breast cancer cells would survive treatment with MEK inhibitors, Dr. Korn says. In analyzing the performance of the MEK inhibitors, researchers noticed that a similar pathway, identified by the activity of an enzyme called PI3-kinase, had been activated. So, of course, we decided that we would try blocking the PI3-kinase pathway as well, assuming that simply blocking both pathways would work, Dr. Korn said.

However, combining the MEK inhibitors with a PI3-kinase inhibitor resulted in cells even more steadfastly resolved to stay alive.

That is when we dec
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Contact: Greg Lester
greg.lester@aacr.org
267-646-0554
American Association for Cancer Research
Source:Eurekalert

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