Abstract A127: Long-term cell culture models enable drug response determination for epigenetic therapeutics.

There has been renewed interest in the field of cancer epigenetics from the pharmaceutical and biotech sectors owing to the discovery of druggable epigenetic modulators that undergo oncogenic mutation and thus represent attractive cancer drug targets. A challenge in this field has been that inhibition of some epigenetic targets results in a significantly delayed drug response that is not revealed by conventional, short-term cell growth assays. We therefore set out to define the two- and three-dimensional assay conditions necessary to yield robust cell line profiling data for therapeutics requiring an extended assay duration. The Eurofins Panlabs’ OncoPanel is a collection of 240 genomically characterized cell lines for which doubling times have been meticulously recorded and compiled over the last several years. Using historical doubling times to compute seeding densities, we demonstrate here that subconfluent, exponential growth can be achieved in the majority of OncoPanel cell lines over the course of 6- or 10-day, two-dimensional growth assays. The EZH2-selective inhibitor, GSK343, elicits a drug response that is dependent both on assay duration and EZH2 mutational status, whereas other less targeted inhibitors show little or no preference for either condition, illustrating the utility of this assay. Similar results were obtained using three-dimensional tumor spheroid assays. Collectively, these data demonstrate the advantages of cell line profiling under long-term assay conditions when drug response reflects a protracted mechanism of action. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):A127. Citation Format: Jim Hnilo, Katie Snead, Karen Bernards, Brian Nelson, Keith McKinley, Kate Waikins, Jonathan M. Crane, Usha Warrior, O. Jameel Shah. Long-term cell culture models enable drug response determination for epigenetic therapeutics. [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 A127.