Abstract B19: Innovative tools to evaluate genetic targets and the efficacy of novel cancer therapeutics.

More predictive small animal models for compound and genetic target assessment are needed to improve development of more efficacious drugs. For assessment of novel cancer therapeutics we have developed an in vivo and ex vivo bioluminescent imaging platform to evaluate compound efficacy. In these mouse models orthotopic tumor grafts are being used that are more relevant with respect to host-tumor interactions, display metastatic potential and allow the evaluation of responses to novel therapeutics. These models closely mimic the progression of human disease and allow quantitative analysis and high throughput in vivo assessment of potential anti-tumor activity. In addition we will present an oncology platform using mouse models for breast cancer. The Brca1/p53 breast cancer model resembles hormone receptor- and ERBB2-negative (“triple-negative”) mammary carcinomas and shows responses to therapies similar to humans, including the emergence of drug resistance. We will present an orthotopic allograft system using primary tumors from Brca1/p53 deficient mice to allow the generation of cohorts developing breast cancer. These grafted mice can readily be used for testing of novel therapeutics in a tumor model resembling human disease. Finally, we will present a transgenic RNAi system that can be used for studying the loss-of-function of target genes. We will present how this system can be used to develop novel disease models and how potentially this model can be combined with disease models to study the genetic loss of a drug target in an established disease state. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr B19.