November 13, 2008

Researchers Make Breakthrough On Breast Cancer Drug Resistance

Scientists in the UK published a study on Wednesday claiming they have figured out why some women develop resistance to the most commonly used breast cancer drug, something that raises the risk their tumors will return.

Jason Carroll of Cancer Research UK in Cambridge, who led the study published in the journal Nature, said the findings could lead to new tests to determine which women are not likely to benefit from tamoxifen and who should be given other drugs.

Carroll said the information could be used to predict which patients will respond to tamoxifen and more importantly which ones won't.

"It gives us an idea of what we should be making drugs against."

The American Cancer Society says breast cancer is the leading cause of cancer deaths among women worldwide. They estimate about 465,000 women died of breast cancer globally in 2007, and 1.3 million new cases were diagnosed.

But early detection through mammography screening and better-improved treatment has contributed to declining death rates from breast cancer in developed countries.

The drug Tamoxifen is given to most women for five years after they are diagnosed with breast cancer to prevent the disease from returning, but some women develop resistance, which means their tumor is more likely to recur.

The researchers said the drug works by blocking estrogen from causing wild cell growth in breast cancer by switching certain genes on, but how this exactly happened was unknown.

Carroll said previous understanding of why this occurred could be compared with trying to fix a broken car without knowing how the engine worked. "Now we understand how all the engine parts operate and we can try to think about ways to make repairs."

The researchers investigated what was happening in genes known to play a key role in breast cancer by using microarrays, or gene chips, to scan millions of DNA sequences.

They said for tamoxifen to work properly it has to block a gene called HER2, which it does by using a control switch hidden within the gene itself.

But a protein called Pax2 must keep the switch in the off position for this to happen"”something that appears to fail for women who develop resistance.

Carroll said the findings mean some women should potentially be directly given other drugs currently on the market such as Genentech's Herceptin or aromatase inhibitors like AstraZeneca's Arimidex.

"It turns out we knew where the genes were but finding out where the switch was located was the difficult part," Carroll said. "Pax2 is the handle that keeps the switch off."


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