Abstract CN03-01: Drug testing in genetically engineered murine models.

Abstract

Abstract Traditional xenograft testing has a poor track record of predicting the efficacy in humans of a novel anticancer compound. Autochthonous tumors occurring in genetically engineered mice more faithfully recapitulate some aspects of human cancers, and therefore may have advantages for preclinical efficacy assessment. The UNC Lineberger Mouse Phase I Unit (MP1U) was founded to allow for medium-throughput testing of novel therapeutics in credentialed cancer GEMMs. The MP1U harnesses the power of murine genetics to produce multi-allelic cancer models featuring autochthonous tumors with physiological tumor-stroma interface and an intact immune response. Promising anticancer compounds are tested alone and in combination in these models, using cohort sizes comparable to human Phase II trials (15-50 subjects per treatment). Agents are considered "active" if they induce sustained and pronounced tumor regression, whereas tumor growth inhibition (TGI) is not considered predictive of human efficacy. Pharmacokinetic and pharmacodynamic assessment is included in efficacy trials, as is serial tumor imaging if needed. The goal is to make testing in the MP1U as close to human Phase I/II anticancer trials as possible, while still taking advantage of the powerful experimental features of murine tumor models. Results of testing with a variety of novel agents will be presented to illustrate the promise and power of GEMM testing. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):CN03-01. Citation Format: Norman E. Sharpless. Drug testing in genetically engineered murine models. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr CN03-01.