Abstract 2794: Ex vivo chemoresponse assay using patient-derived tumor xenografts in combination with high content imaging platform as models for oncology drug development.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Current strategies for developing new anticancer drugs rely heavily on preclinical testing in cancer cell lines and their derived in vivo cell line xenograft models. The value of a predictive assay is heavily dependent on the extent to which it can recapitulate the biology of disease. It has been reported that heterogeneity of cell populations within the tumor microenvironment has significant correlation with the efficacy of any treatment regimen. Cell line models fail to recapitulate the heterogeneous nature of tumor. The purpose of this study was to investigate whether the use of patient-derived primary tumor cells (PTC) could be expanded as xenografts for in vitro chemosensitivity assays to predict clinical outcomes in anticancer drug testing. We have developed preclinical cancer models using PTCs grown in 3D cultures that better mimic in vivo conditions. One of the disadvantages of using patient derived cells is the limited number of cells available from biopsy samples. We utilized patient-derived xenografts (PDX) as a strategy to expand the human tumor cells in mice, while taking efforts to retain the actual tumor biology of the patient. We used high content imaging to evaluate colony segmentation, morphological features, proliferative and apoptotic endpoints to determine efficacy of oncology drug candidates. We conducted a retrospective study using PTCs from solid tumor indications including endometrial and lung to evaluate the correlation between various models and usefulness in predicting the outcome of a specific drug candidate. Our results indicate that PDX models in combination with 3D PTC models have predictive value and enable secondary interrogation beyond single agent anti-proliferative activity to better profile the antitumor activity of targeted agents. Improved preclinical models are required to advance our understanding of the molecular aberrations that underpin cancer and are critical for developing and deploying targeted therapies that will improve patients’ lives. Citation Format: Mansi Garg, Martin Vo, Jill Ricono, Thomas Broudy, Cyrus Mirsaidi, Kesavan Nair Praveen. Ex vivo chemoresponse assay using patient-derived tumor xenografts in combination with high content imaging platform as models for oncology drug development. [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 2794. doi:10.1158/1538-7445.AM2013-2794