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Cell marker identifies patients who are more likely to respond to taxol


Researchers at The University of Texas M. D. Anderson Cancer Center have found a potential predictor of response to the chemotherapy drug Taxol, which is commonly used before or after surgery for stage I-III breast cancers, even though only a subset of women ultimately benefit from this treatment.

Patients whose breast cancer cells have lost their ability to express a protein called "tau" are twice as likely to have a good response to Taxol treatment, the researchers report at the annual San Antonio Breast Cancer Symposium meeting.

The finding makes sense because tau promotes the assembly of microtubules, which provide structure to the cell and help it divide. Taxol works by binding to microtubules to form an inappropriately stable structure which ultimately leads to cell death. "In the absence of tau, Taxol stabilizes microtubules more easily," says the study’s lead researcher, Lajos Pusztai, M.D., Ph.D., an associate professor in the Department of Breast Medical Oncology.

If validated in larger studies, the finding suggests that tumor tissue could be screened to predict if it will respond to Taxol, says Pusztai. "If it doesn’t, perhaps other chemotherapy regimens would work better."

The results also suggest a way to improve the use of Taxol, Pusztai says. "If you block the effect of tau with an agent, you could possibly increase the effectiveness of Taxol in more patients, making them super responders."

The researchers came up with their discovery after examining breast cancer biopsy samples taken from 82 patients, 21 of whom had a complete disappearance of their cancer after Taxol-containing treatment. They looked at the difference between these responders and non-responders in 22,000 genes, and found that tumors were highly sensitive to treatment that had low levels of tau messenger RNA (mRNA) expression in their cancer cells. This observation was confirmed by examining tau protein expression using a routine pathological assay, immunohistochemistry, in 122 additional patients. Then, research in breast cancer cell lines in the laboratory were undertaken to look at how low expression of tau leads to increased sensitivity to Taxol.

Pusztai says that about 25 percent of all patients show very high sensitivity to the Taxol-containing chemotherapy, and respond with complete disappearance of cancer after treatment.

"Assessment of tau expression at the time of diagnosis could identify a group of patients who are at least twice as likely to have high sensitivity to the treatment," he says. "The rest of the patients may not benefit much from the drug because none of the patients who had high levels of tau mRNA expression in their cancer experienced complete response to therapy.

Before routine use of such a test can be recommended, investigators say these findings will need to be examined in a larger, randomized study to accurately determine the clinical value of tau as a predictive marker.

Nancy Jensen | EurekAlert!
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