Abstract A13: Characterization of CRC primary explant models in comparison to standard human tumor cell-line-derived CRC xenografts.

Primary tumor xenograft models (PTX) are established in immunodeficient mice by implantation of material directly from patient tumors. These models are propagated in vivo so that they are not subjected to additional selection pressures within tissue culture. The models reputedly reflect a greater genetic diversity of disease than can be recapitulated within tumor cell line derived xenografts and may have morphological differences. Consequently, such models may be of greater relevance for the evaluation of drug efficacy. To verify differences versus cell line derived xenograft models, we have examined samples of 42 CRC PTX models, derived from Dukes stage A-D tumor samples, which were obtained from European contract research organisations) Characterisation included analysis of common genetic mutations (KRas, BRAF, PI3Ka, PTEN, P53 and APC), mRNA expression via microarray platforms (Affymetrics HG_U133_plus_2), high-throughput RT-PCR of specific probes (mouse and human) to examine stromal genes, and the activation of particular proteins using reverse phase antibody arrays and immunohistochemistry. Comparisons were made with 6 commonly used CRC cell line derived xenografts. The PTX models overall represent a broader range of molecular pathology - for example the inclusion of wild-type Kras tumors. Histopathological characterisation also confirmed that the PTX models have a higher stromal content that is routinely observed in cell line derived xenografts, and a more complex morphology with higher tumor cell differentiation. PTX models may potentially complement drug discovery activities by providing a wider platform in which to test preclinical hypotheses - based upon a defined biological mechanism and/or a genetic determinant of sensitivity. 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 A13.