Abstract 1568: Evaluate the efficacy of new therapeutics using advanced metastatic mouse models.

Abstract

Abstract Metastasis, the spread and growth of tumor cells to distant organs, is usually a final and fatal step in the progression of solid malignancies. Preclinical test of the new anti-cancer therapies that could mimic the disease present in most clinical trials asks for robust metastatic models than just the subcutaneous models. We sought to establish and validate a panel of experimental (i.v. inoculation) and spontaneous (orthotopic inoculation) mouse models with high metastatic potential and varied tissue tropism in different types of cancer models, covering colorectal, liver, prostate, breast, pancreatic cancer and melanoma. The responsiveness of metastasis to several therapies that are proved to be clinically effective or ineffective was investigated. A higher predictive power of the metastatic models was demonstrated compared with the corresponding subcutaneous models. By means of the transcriptomic analysis of the paired primary tumor population and the distant lung metastasis population in 5 orthotopic tumor models, we identified the gene signatures that differentiate the two populations in different tumor types. Our signature was also compared with the clinical relevant gene signatures correlated with lung metastasis risk. Several genes are concordantly expressed in both signatures and are biologically meaningful. Overall, given the higher predictive power and the clinical relevance, the use of the metastatic mouse models constitutes an effective and important strategy to preclinically evaluate the efficacy of new therapeutic regimens. Citation Format: Juan Zhang, Sheng Guo, Jie Cai, Yanmei Sun, Guanping Mao, Zhun Wang, Lan Zhang, Ying Jin, Qian Shi, Taiping Chen. Evaluate the efficacy of new therapeutics using advanced metastatic mouse models. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1568. doi:10.1158/1538-7445.AM2013-1568