Abstract 2036: OncoPanel 3D: High-content characterization of 240 three-dimensional tumor spheroids for drug response profiling and biomarker discovery

Abstract

Abstract While drug response profiling of cancer cells in two-dimensional culture has been a mainstay of predictive biomarker discovery and anti-cancer drug development, there are aspects of tumor biology that are not replicated in a two-dimensional cell culture environment. This is particularly true for solid tumor models where the three-dimensional organization of the tumor creates distinct, regional microenvironments that influence drug response. For example, as the radius of solid tumors approaches the diffusion limit of oxygen and other nutrients, the tumor core becomes hypoxic and accumulates metabolic waste products, resulting in cell death through mechanisms involving apoptosis and necrosis. Moreover, without proper vascularization, the tumor interior also exhibits increased interstitial pressure, which limits drug penetration into the tumor. We have characterized the three-dimensional growth of 240 cancer cell lines from various tumor origins by high-content imaging. This characterization involves the growth of tumor spheroids over 14 days and an assessment of tumor hypoxia in each model. The genomic traits associated with spheroid formation are also defined through genomic analysis. Finally, we provide validation and drug response data for several standard-of-care cancer therapeutics in pre-formed, three-dimensional tumor spheroid models. Drug profiling of this three-dimensional cell line panel offers new insights into drug response and can be used to prioritize drugs with improved tumor penetration or those with otherwise improved activity in three-dimensional models. Citation Format: Katie Snead, Jim Hnilo, Karen Bernards, Jonathan M. Crane, Brian Nelson, Alison R. Angione, Keith McKinley, Kate Waikins, O. Jameel Shah. OncoPanel 3D: High-content characterization of 240 three-dimensional tumor spheroids for drug response profiling and biomarker discovery. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2036. doi:10.1158/1538-7445.AM2014-2036