Abstract 1258: Pooled-analysis of response markers in cancer cell lines treated with tumor treating fields

Abstract

Abstract Low intensity, intermediate frequency alternating electric fields (TTFields) exert an inhibitory effect on numerous cancer cell lines with some variability in the response. The goal of the present study is to compare characteristics of cell lines based on their response pattern to TTFields and to identify response markers. Forty-five different human cancerous cell lines were treated for 72 hours with TTFields at optimal cell-specific frequency at the same nominal intensity (1.7 V/cm). Cytotoxicity and clonogenic potential were determined. Functional analysis of differentially expressed genes and mutations associated with response to TTFields was performed based on the Cancer Cell Line Encyclopedia (CCLE) database. Sensitivity to TTFields was compared with pharmacological profiling (CCLE). The cytotoxic response to TTFields was found to be distributed around an average of 50% with (ranging between 14% and 86% reductions in cell counts). The clonogenic effect varied between no effect and 88% reduction in the number of colonies. Increased sensitivity to: Lapatinib, PHA-665752 and PLX-4720 was common in the group of cell lines which were more highly responsive to TTFields. Functional analysis of cell line gene expression and mutation data revealed enriched pathways related to DNA damage repair response, cell migration, hypoxia signaling and oxidative stress. This analysis of cancerous cell line response to TTFields define the optimal frequency to be applied for each cell line and demonstrates the broad effectiveness of TTFields in cells. The role of the specific mutations associated with TTFields response should be further explored in additional studies. Pharmacological profiling may offer a rational for combining specific agents with TTFields. Citation Format: Gitit Lavi Shahaf, Moshe Giladi, Rosa S. Schneiderman, Karnit Gotlieb, Einav Zeevi, Yaara Porat, Mijal Munster, Uri Weinberg, Eilon D. Kirson, Yoram Palti. Pooled-analysis of response markers in cancer cell lines treated with tumor treating fields [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1258.