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New data improve understanding of breast cancer's multiple varieties
Date:5/3/2012

stimuli.

To clarify this issue, they used a genetic mechanism to block the AP-1 pathway in mice and cell culture. The researchers report that inhibiting AP-1 enhanced the effects of tamoxifen and delayed the development of tamoxifen resistance. Their data suggest that specific drugs with 'AP-1 inhibitory' effects might be useful in combination with available endocrine agents to develop new, more efficacious treatments.

"Fully understanding the biology behind endocrine resistance is the first step to design new drugs. I think that our data represent such a step forward," Dr Malorni said. "At the same time, our data might be helpful in deriving new biomarkers that could identify patients at higher risk of developing endocrine resistance. This might be an important contribution as today we are able to only partially predict response to endocrine treatment with the available biomarkers."

The researchers propose that endocrine resistance develops when the estrogen receptor 'switches' from its classical direct binding to specific estrogen responsive elements in the tumor genome, to an indirect DNA binding program via AP-1.

"In this light, AP-1 cooperation with estrogen receptor might be considered as a fundamental feature of the endocrine-resistant breast cancer cell. We cannot exclude, however, that AP-1 activity independently of ER is also important. More studies are needed to dissect these different mechanisms," Dr Malorni said.

"I hope that our data could stimulate researchers in this field to consider in their studies the 'switch' in estrogen receptor activity that we are proposing," the researcher added. "For instance, common techniques to evaluate estrogen receptor activity in vitro rely only on measurements of ERE-related functions. Our data suggest that this might be an incomplete view that needs to be implemented with measurements of other estrogen receptor functions as well, such as those that are related to AP-1.
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Contact: Vanessa Pavinato
media@esmo.org
European Society for Medical Oncology
Source:Eurekalert

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