Abstract 1180: Quantifying melanoma drug resistance and tumor heterogeneity by live cell interferometry

Abstract

Abstract Melanoma is the most aggressive type of skin cancer. Tumor heterogeneity and drug resistance are significant obstacles to survival benefits from mutation-targeted therapy. Over 50% of metastatic melanomas harbor V600BRAF mutations. Targeting of MUTBRAF melanoma with BRAF inhibitor monotherapy or the combination of BRAF and MEK inhibitors leads to a high rate of initial responses, but adaptive and acquired resistance frequently leads to clinical relapse. Although the presence of V600BRAF mutations guides the selection of therapy with MAPK inhibitors, methods to track preexisting and adaptive resistance and thereby predict response patterns, or to use this new information to modify therapy, are still lacking. Here, we aimed to develop a rapid, massively parallel tumor cell profiling method, based on Live Cell Interferometry (LCI), to quantify heterogeneous single tumor cell responses and emergent drug resistance. LCI is an ex vivo imaging approach that quantifies changes in total cell biomass, biomass motion, or cell stiffness over time. We report a novel high-throughput screening version of the LCI platform, HSLCI, which rapidly profiles changes in biomass in BRAF inhibitor (BRAFi)-sensitive, parental melanoma cell lines and their isogenic, BRAFi-resistant sub-lines. We show reproducible results from two different HSLCI platforms at two institutions and generate biomass kinetic signatures capable of discriminating between BRAFi-sensitive and -resistant melanoma cells within 24 hours. Our measurements require no fluorescence or dye labeling and are faster than field-standard growth inhibition assays. The accuracy and speed of HSLCI in profiling tumor cell heterogeneity and therapy resistance are promising features of potential tools to guide patient therapeutic selections. Citation Format: Kevin A. Leslie, Dian Huang, Graeme Murray, Daniel Guest, Irena J. Roy, Marco Piva, Gatien Moriceau, Roger S. Lo, Michael A. Teitell, Jason C. Reed. Quantifying melanoma drug resistance and tumor heterogeneity by live cell interferometry [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1180.