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Novel Human Tissue Transgenic Cancer Model May Offer Significant,Advance Toward Accurately Modeling Human Cancer

e cancer gene candidates, determine their biological roles in various stages of cancer progression, and test targeted therapies directed against specific genetic lesions found in human breast cancers. We have been very encouraged by the similarity to human patients in both histological appearance and response to agents like Herceptin(R) (trastuzumab)."

AVEO's Proprietary Human Tissue Transgenic HIM Model

AVEO sought to generate an in vivo model of human breast cancer in mice (HIM) by employing a unique tissue recombinant system comprised of human breast stromal cells and epithelial organoids engineered with defined transgenes. Depending on the combination of transgenes employed, the reconstituted human breast tissue developed into preneoplastic lesions (Carcinoma In Situ or CIS) or to invasive adenocarcinomas. Importantly, despite using the same set of genetic alterations, significant variation in tumor phenotype was observed among tumors depending on the source of donor organoids. This last observation suggests that differences in the genetic makeup individual donors may influence the development and progression of these tissue transgenic breast tumors. Because this observed variation is similar to what is seen across human breast cancer patients, AVEO is generating a large number of individual tissue transgenic breast tumors to create a population of tumors in which to explore the relationship between this variation and response to anti-cancer agents.

Ha-Ngoc added, "In addition to capturing variation across a population, the ordered progression observed in this model also provides an opportunity to test drug efficacy in treating early stage tumors. We believe the ability to create genetically manipulated human tumors that develop entirely in an in vivo context may provide a significant advance toward accurately modeling human cancer, which will enable AVEO to guide our clinical development and generate more effective, targeted treatments for
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