Breast Cancer Research Shifts to Targeting of Drugs to Patients

By Blank, Christine | Drug Topics, November 4, 2002 | Go to article overview

Breast Cancer Research Shifts to Targeting of Drugs to Patients


Blank, Christine, Drug Topics


Researchers at the Department of Defense's annual Era of Hope Breast Cancer Research Program meeting in Orlando, Fla., shared new techniques to target the right patients to receive cancer drugs, as well as preliminary research on the development of more effective medicines.

Some of the DOD's $150 million funding for breast cancer research in 2002 focused on genetic testing for better drug targeting. For example, initial research at Baylor College of Medicine and the Methodist Hospital, both in Houston, is showing that gene expression profiling can determine, with 83% accuracy, which patients will respond to docetaxel (Taxotere, Aventis), one of the two main drugs used to treat breast cancer.

"A test that identifies likely responders and nonresponders may eventually improve outcomes, by routing the best candidates to docetaxel therapy early and sparing other women exposure to a treatment that will be ineffective for them," said Jenny Chang, MD., assistant professor at Baylor.

The gene expression technique involved using a gene chip that measures 12,000 human genes. When gene expression was analyzed without knowing the treatment result, two distinct patterns emerged. Then, when treatment response to docetaxel was evaluated, 10 of the 13 patients with the first pattern had good responses, while 10 of the 11 patients with the second pattern were resistant to the treatment, giving an 83% predictive accuracy.

Baylor College, along with the University of Minnesota and a college in London, has begun a similar study of 100 patients, testing both docetaxel and AC chemotherapy-Adriamycin (doxorubicin, Pharmacia) and cyclophosphamide. Chang is also in the midst of genetic testing that will identify pathways that lead to resistance.

"If you can find out what's resistance, you can develop smart drugs that overcome the resistance," she said. She is hoping to get the results back within a year.

In preliminary work on improving drug pathways and resistance researchers at the University of Cincinnati College of Pharmacy found that folate conjugates combined with the cytotoxic agent doxorubicin appear to provide a more effective treatment of drug-resistant breast cancer than does administration of uncojugated drugs.

Researchers are also looking for more effective and less toxic alternatives to popular breast cancer drugs. Preliminary tests of taccalonolide A, the first natural steroid to exhibit microtubule-stabilizing activity suggest that it should be further evaluated for efficacy in preclinical models of breast cancer, according to scientists at the Southwest Foundation for Medical Research.

Some of the most effective breast cancer drugs target cellular microtubules, including paclitaxel and docetaxel, but many patients develop multidrug resistance. …

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