AVEO Pharmaceuticals, Inc. has announced findings from its novel human-in-mouse (HIM) cancer model system, in which AVEO successfully created invasive human tumors from primary human breast tissue that develop over time in mice and mimic human tumor behaviors and response.
The findings were published this week in the Early Edition of the Proceedings of the National Academy of Sciences .
More than 95 percent of oncology drugs entering the clinic fail, due in large part to the lack of predictive animal models in the preclinical development phases. AVEO scientists have developed a sophisticated cancer biology platform that provides models of human cancer more relevant than traditional mouse models known as xenografts. In the AVEO HIM model, normal human breast tissue is engineered to express oncogenes and is then introduced into mice where it forms human breast tissue in the mouse mammary microenvironment. The tumors which then develop spontaneously acquire common and distinct mutations during tumor progression. This process results in human tumors in mice that reflect their human counterparts in that they differ slightly from one instance to another, exhibiting natural genetic variation akin to that seen in patients.
"Historically, the xenograft models created to analyze how human cancers behave have not been accurate predictors of human responses to various therapeutic agents," said Robert A. Weinberg, Ph.D., member, Whitehead Institute and professor of biology, MIT. "In contrast, tumor development in the HIM model proceeds through defined histological stages of hyperplasia, from ductal carcinoma in situ (DCIS) to invasive carcinoma. Moreover, HIM tumors display characteristic responses to a targeted therapy known to be effective in humans, specifically 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."