Abstract 5075: Phenotypic human tumor cell line profiling and predictive biomarker analysis for epigenetic inhibitors

In recent years, epigenetic target inhibitors have emerged as viable therapeutics for treating various types of cancers. Testing of the epigenetic inhibitors in cell proliferation assays revealed that inhibition of many epigenetic targets resulted in a significantly delayed drug response that is not revealed by conventional, 72-hour cell growth assays. OncoPanel LT™ from Eurofins Pharma Discovery Services is developed specifically for evaluation of compounds with a protracted mechanism of action, and consists of a large collection of cell lines with broad cancer type and subtype representation, and extensive genomic characterization. We have tested decitabine, a DNA methyltransferase inhibitor, panobinostat, a histone deacteylase inhibitor, GSK-343, an EZH2 inhibitor, GSK-J4, a JMJD3/UTX inhibitor, and JQ1, a BRD2/3/4 inhibitor in OncoPanel LT™. These epigenetic inhibitors were incubated for 10 days with more than 200 human tumor cell lines and the inhibition data were analyzed to determine IC50, EC50, and GI50 values. These inhibition data, as well as the genomic features of the cell lines, were utilized to perform univariate genomic analysis to identify predictive biomarkers of response. We will discuss the activity of compounds against this cell line panel, as well as statistically significant biomarkers of response, based on the univariate genomic analysis. Citation Format: Usha Warrior, Jesse J. Parry, Samantha C. Burkart, Lee R. Cavedine, Alyssa M. Cracchiolo, Brogan A. Epkins, Steven M. Garner, Timothy J. Sindelar, Charles R. Wageman, Alastair J. King. Phenotypic human tumor cell line profiling and predictive biomarker analysis for epigenetic inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5075. doi:10.1158/1538-7445.AM2017-5075