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Molecular fingerprint of breast cancer drug resistance can predict response to treatment

Published on September 25, 2007 at 1:47 AM · No Comments

A way of predicting which patients will respond well to treatment with a common chemotherapy drug used in breast cancer was unveiled at the European Cancer Conference (ECCO 14).

Dr Iain Brown, from the University of Aberdeen, Aberdeen, Scotland, told the conference that he and his colleague, Dr Andrew Schofield, had identified two genes that could identify which cells would be resistant and which would respond to docetaxel.

Docetaxel is one of the most effective chemotherapy treatments in advanced breast cancer. It works by binding to cell components called microtubules, and stabilising them so that they do not disassemble. They then accumulate within the cell and bring about apoptosis, or cell death. “However, up to half of all patients treated with this drug will develop resistance, and hence the treatment will fail,” said Dr Brown.

The scientists decided to look for a specific genetic make-up in patients where docetaxel treatment had failed, in the hope that this might explain why they became resistant to the drug. They used micro-array analysis, a technique that allowed them to look at every known gene in our cells at once, to identify genes that were significantly associated with such resistance.

“By going back to the laboratory, using breast cancer cell lines, we can eliminate much of the variation in gene expression found in different patients, and thus remove a lot of ‘background noise’,” said Dr Brown. “We developed a unique model of docetaxel resistance in breast cancer from two different cell lines made resistant to the drug by exposing them to increasing concentrations of the drug. This model has also allowed us to test cells which are resistant to low levels of the drug and cells which are resistant to high levels.”

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