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Breakthrough model for human cancer may improve development of cancer drugs; study in PNAS
Date:4/6/2009

ly Herceptin. This represents a big step forward in developing xenograft models that will accurately predict patient responses to agents that are in preclinical development. The HIM model is an exciting, experimentally tractable human in vivo system that holds great potential for advancing our basic understanding of cancer biology and for the discovery and testing of targeted therapies."

By employing a tissue recombinant system and a gene transduction system, researchers assessed the in vivo biological consequences of specific genetic alterations in the reconstituted breast tissue. Introduction of different combinations of oncogenes, such as HER2, KRAS, PI3 kinase and p53, into the tissue enabled the researchers to dissect the contribution of each gene to human tumor formation in the model.

The authors also demonstrated the utility of the HIM models for drug efficacy testing by treating the HER2 driven breast tumors with different HER2 antagonists. The resulting potent inhibition of HIM tumor growth correlates with what has been observed in the clinic.

"With the increasing knowledge of specific genetic alterations in breast cancer, there is now a significant opportunity to correlate activity of anticancer agents with specific genetic alterations in tumors," added Murray O. Robinson, Ph.D., senior vice president, oncology at AVEO. "Our proprietary models provide a defined genetic context in which to validate cancer gene candidates, determine their biological roles in various stages of cancer progression and test targeted therapies. We have been very encouraged by the similarity to human patients in response to widely used breast cancer agents."


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Source:Eurekalert

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