Working group on high-throughput drug and target discovery started at Fraunhofer ITEM in Regensburg
The low success rate in generating predictive disease-relevant cellular models for most cancer types remains a key technical obstacle in the discovery and development of novel therapeutics in oncology. The Working Group on “High-throughput drug and target discovery” was founded at Fraunhofer ITEM in Regensburg in September 2017 to address some of these challenges. The newly established group aims to generate a panel of patient-derived preclinical in vitro-models for multiple cancer types and to subsequently use them in high-throughput drug and target screening campaigns.
Initially an automated high-throughput platform will be established to systematically test and optimize cultivation and expansion conditions of primary human tumor cells. Different extracellular matrix compositions, culture media, nutrients, growth factors, hormone supplements, pharmacological compounds, exosomes and feeder cells will be tested in multiple combinations under tumor-like microenvironments to improve the success rate of culturing primary tumor cells. On the long-term, such acquired knowledge will be employed in culturing and expansion of circulating and disseminated cancer cells, as well as growing tumor cells in their specific metastatic niches.
Upon successful development of a panel of patient-derived preclinical models, these cells will be adapted for high-throughput assays and used in pharmacological and genetic screens to identify disease-relevant genes, pathways, therapies and diagnostic tools. Large-scale loss of function screens using siRNA and/or gRNA CRISPR-Cas9 libraries in these cells may allow systematic identification of novel drug targets for various cancer types. Similarly, novel cancer therapeutic lead structures can be identified by functional screening of compound libraries in these cells. This approach will be of particular value for highly aggressive tumor entities for which effective therapies are yet lacking (e.g. small-cell lung cancer).
Fraunhofer ITEM in Regensburg has recently signed a collaboration agreement with Assay.Works GmbH (BioPark Regensburg), which possesses expertise in assay development and drug discovery services for the development of disease-relevant cellular assays for high-throughput screening. Within the framework of this collaboration, Fraunhofer ITEM scientists in Regensburg will have access to the state-of-the-art high-throughput screening infrastructure of Assay.Works, such as automated cell culture, robotic liquid handling stations, nanoliter dispensing, plate readers and automated high-content imaging systems, but also a collection of diverse and focused small-molecule as well as genome-wide siRNA libraries.