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Accelerating Discovery of Novel Drug Combination Therapies Using High-Throughput Combination Profiling

SLAS, San Diego, CA, USA
January 20, 2014

Drug combination treatments have been widely recognized as an essential therapeutic strategy for chronic diseases such as cancer. A successful combination approach enhances clinical efficacy through drug synergistic effect, improved therapeutic window by reducing effective clinical dosage, and overcoming or delaying the onset of drug resistance.

In order to rapidly identify effective and disease-specific combinations across a large spectrum of drug candidates preclinically, in vitro cell-based phenotypic assays remain the most viable approach. However, the challenges of developing disease-relevant assay endpoints and industrial-scale screening remain.

In recent years, large scale genomic and mutation analysis of clinical tumor biopsies has facilitated the sub-classification of tumor sub-types within cancers. This has helped the stratification across in vitro tumor cell panels to align each sub-panel with the corresponding clinical segment, improving the translation of in vitro profiling data to the clinic.

This poster presents the high-throughput combination capability implemented within Oncology iMed in AstraZeneca using such in vitro tumor cell panels. It consists of a novel workflow tool, high speed acoustic combination dosing and imaging instrumentation, as well as a new combination data analysis platform developed in collaboration with Genedata, the Compound Synergy Extension to Genedata Screener®.

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