Category: Assay Development and Screening
Cancer therapy is increasingly moving towards individualized care and therapy, but there are still big 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, 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 funtionally profile the responses of primary cancer cells to a comprehensive clinical oncology and signal transduction inhibitor drug collection of 528 compounds.
The results of these assays are in turn 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 individual cancer-selective targeting drug combinations and their predictive biomarkers, which can be explored in the clinic by our clinical collaborators who can, when applicable, use the information to guide the treatment of the individual patient.
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.
In summary, we describe here how acoustic dispensing is enabling functional precision medicine testing in our cancer individualized systems medicine program to (1) generate consistent and configurable assay-ready plates and determine how this affects data quality, (2) flexibly prepare drug combination testing plates, (3) dispense reagents and cells to the assay plates, and (4) perform ultra-miniaturized follow-up assays on the cells from DSRT plates. This platform enables us to generate consistent biological and clinically relevant data.
Laura Turunen– Laboratory Coordinator, FIMM /High Throughput Biomedic, Helsinki University, Uusimaa, Finland
FIMM /High Throughput Biomedic
Helsinki University, Uusimaa, Finland
Laura Turunen has worked at FIMM High Throughput Biomedicine (HTB) team for eight years as automation specialist and compound manager. She's responsible for the various automated equipment, including various liquid handlers and dispensers, and the compound collections consisting approximately 130 000 compounds from commercial sources. She's also planning and running various projects for users of the HTB lab services.