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Old 04-22-2005, 11:22 PM   #1
Merridith
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Measuring Enzymes At End Of Cancer Pathway Predicts Outcome Of Tarceva, Taxol

Researchers at The University of Texas M. D. Anderson Cancer Center have developed a way to test whether the new targeted therapy Tarceva and the widely used chemotherapy drug Taxol are effectively killing tumor cells. They say that with further refinement, the test may make it possible to accurately assess whether patients are responding to these agents, as well as potentially others, within days of beginning therapy.

In two different studies being presented at the annual meeting of the American Association for Cancer Research (AACR), the research team will describe how the test measures the activity of several members of the cyclin-dependent kinase (CDK) family of enzymes, which are the triggering molecules that allow a cell to grow and divide. CDK cell cycle enzymes are the end target of numerous cellular pathways that are involved in cancer development and progression, the researchers say..........

......Taxol, used to treat a wide spectrum of cancers, works by interrupting the reorganization of the cell that is necessary if it is to divide. While it was known that the primary effect of the drug is to interfere with assembly of the spindle that pulls nuclear chromosomes apart during cell division, Ueno and his colleagues have recently reported that increased activity of CDK1 correlated with a cell's sensitivity to Taxol.

The CDK enzyme plays a role in cell division, and researchers believe that it functions in part as a monitor of cell cycle activity. Ueno theorizes that if something goes wrong during division - such as if Taxol is interrupting spindle assembly - CDK will become more active in an attempt to correct the problem.

Working with the Sysmex Corporation of Kobe, Japan, the researchers devised a test to measure CDK activity and the expression, simultaneously.

They found that monitoring of two isotypes of CDK activity accurately predicted which tumors would respond to Taxol in the experiments with human breast cancer cell lines and tumor tissues of human xenograft model.

"This provides solid preclinical evidence that we can use toward development of a novel device that can measure CDK activity in human tissue within several hours," Ueno says. He adds that a clinical trial is currently under way that tests CDK activity both before and after patients with breast cancer are treated with Taxol.
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