Abstract 2153: Ex vivo drug sensitivity testing of primary cells for precision cancer medicine

Abstract

Introduction/Purpose: Cancer therapy is increasingly moving towards individualized care and therapy, but there are still gaps between what is known and described on the molecular level about cancers and what is applied in the clinic. In an attempt to bridge the knowledge gap, we at the Institute for Molecular Medicine Finland (FIMM) have set up an Individualized Systems Medicine program that integrates clinical information, molecular profiling and functional information about individual patients’ cancers (Pemovska et al, Cancer Discov, 2013). Central to this program is the Drug Sensitivity and Resistance Testing (DSRT) where we functionally profile the responses of primary cancer cells to a comprehensive clinical oncology and signal transduction inhibitor drug collection of 528 compounds. Methods: Acoustic dispensing platforms are integral to the success of this profiling activity. We have to date produced approximately 3000 drug sets as dose response assay ready plates. The acoustic dispensing allows for making pre-drugged single drug plate sets and/or drug combination plates within hours after sampling of the cells. The plates are also readily sent to researchers anywhere in the world for running comparable assays at other sites. The drugging reproducibility is excellent generating results with correlations of 0.98 or higher in replicate assays. We have developed in-house software solutions to aid these processes: a script for quick creation of transfer list for combination plates and automated analysis pipelines with web-based software interfaces to enable the screening biologists to analyze the screening results effectively. Results: The results of these assays are used to explore and understand cancer biology in terms of druggability, functional heterogeneity and mechanism of drug response and resistance. The profiling data can be used to stratify and position the relevance of specific drugs in different diseases and has been used to identify novel clinically relevant activities of existing and investigational drugs (see e.g. Pemovska et al, Nature, 2015). This information is further utilized to establish hypotheses on drug combinations selectively targeting individual cancers and their predictive biomarkers, which can be explored in the clinic by our clinical collaborators to guide the treatment of the individual patient. Conclusions: In summary, we describe our platform for a functional drug sensitivity testing within our individualized cancer systems medicine program, which generates consistent biological and clinically relevant data. Citation Format: Sergey G. Kuznetsov, Alexander Ianevski, Evgeny Kulessky, Karoliina Laamanen, Elina Lehtinen, Maria Nurmi, Swapnil Potdar, Jani Saarela, Katja Suomi, Laura Turunen, Krister Wennerberg, Paivi Tammela. Ex vivo drug sensitivity testing of primary cells for precision cancer medicine [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 2153.