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Lab Studies Predict Outcome With Tarceva, Taxol (From Joyce)

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Also Joyce asked me to post this for her. Thanks again Joyce (endangered but surviving) for sharing, interesting read. Rich

http://www.cancerwise.org/june_2005/dis ... &color=red

Lab Studies Predict Outcome With Tarceva, Taxol

Enzyme Measurement Assesses Breast Cancer Drug Results

A new test has been developed to determine the effectiveness of the popular breast cancer drugs erlotinib (TarcevaTM) or paclitaxel (Taxol®), researchers say. With further refinement, the test may assess a patient’s response within days.

Two studies presented by M. D. Anderson scientists recently at the annual meeting of the American Association for Cancer Research (AACR) focused on several members of the cyclin-dependent kinase (CDK) family of enzymes. CDK prompts cells to grow and divide, causing cancer development and progression.

Previously, no one had accurately tested enzyme function from a human tumor sample, says Naoto Ueno, M.D., Ph.D., an associate professor in M. D. Anderson’s Breast Cancer Translational Research Laboratory and its Department of Blood and Marrow Transplantation. “Our hope is to use this system as a molecular marker to assess whether an anti-cancer therapy is working.”

Sensitivity to Tarceva depends on CDK2

In the first study, M. D. Anderson researchers found that loss of the CDK2 enzyme strongly correlated with a cancer’s sensitivity to Tarceva.

Ten human breast cancer cell lines were exposed to varied doses of Tarceva. Researchers then measured CDK enzyme activity and found tumor cell death was dependent on whether CDK2 activity was repressed.

Development of CDK2 test is needed

“We found the effects of Tarceva were reduced when CDK2 was given back to the cells, so this shows CDK2 is the real target of Tarceva,” he says. “As long as CDK2 is suppressed, the drug works, so developing an accurate test for CDK2 activity would be a boon for delivering individualized therapy to patients.”

Such a test, however, will require patients be given the drug for a short period so the agent’s effect can be assessed. If study results are verified, “a CDK2 test would provide the best marker yet for effective use of Tarceva,” Ueno says.

Scientists profile CDK to predict Taxol effectiveness

A different research team headed by Ueno also found that if activity of several CDK molecules is increased – not decreased as in the Tarceva finding – then Taxol appears to effectively kill breast cancer cells.

Taxol, a chemotherapy that treats a wide spectrum of cancers, works by interfering with the assembly of the “spindle” that pulls nuclear chromosomes apart during cell division. Ueno theorized that if something goes wrong during division, such as if Taxol is interrupting spindle assembly, CDK will become more active to correct the problem.

Tumors respond in lab experiments

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

"They found that monitoring two isotypes of CDK activity accurately predicted which tumors would respond to Taxol in experiments using a human xenograft model (mice with low immune systems injected with human cancer cells).

This provides evidence for developing a device that measures CDK activity in human tissue within several hours, Ueno says. A clinical trial is ongoing to test CDK activity before and after breast cancer patients are treated with Taxol.

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