Mouse models predict chemo treatment response in humans
Researchers at the University of North Carolina at Chapel Hill have found that genetically engineered mouse models are able to predict how humans will respond to different chemotherapy drug combinations used to fight breast cancer.
Using genetically engineered mouse models, or GEMMs, UNC scientists identified biomarkers for challenging molecular subtypes of human breast cancer, including basal-like, luminal B, and claudin-low--types that have few targets and therapies available. These tumors are challenging to destroy because they are usually unresponsive to drugs like Herceptin or aromatase inhibitors. The new report by UNC scientists sheds more like on these tumor subtypes.
"This is a wonderful example of how well chosen mouse models can inform a human disease state. In this case we used years of research to match the models to specific human subtypes, and then treated the animals with therapies identical to what human cancer patients are receiving. We were ultimately able to develop a biomarker of treatment response from the mouse that works in humans," said lead study researcher Charles Perou, a member of the UNC Lineberger Comprehensive Cancer Center.
First, the team developed gene signatures derived from rodents that corresponded to a distinct treatment response. Testing several agents for their predictive potential using data from human patients, the researchers found that one, paclitaxel, exhibited exceptional efficacy. The team then identified gene expression signatures that predicted pathological complete response to the chemotherapy neoadjuvant anthracycline (doxorubicin)/taxane (paclitaxel) therapy in human patients with breast cancer, even among the difficult-to-treat triple-negative patient subset.
Their findings were published in the June 19 online issue of the journal Clinical Cancer Research.
Traditional mouse model research has used mice lacking immune systems into which human tumors or cell lines were grafted, whereas the GEMMs show how cancer develops in the presence of an immune system.
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