ELRIG Drug Discovery 2023 congress will take place in Liverpool next week (October, 18 & 19th 2023). Our project leader Dr. Véronique De Conto will have the pleasure for presenting a poster about High Content Screening in 3D models including the tumoral Extracellular Matrix.
Abstract:
In oncology, 97% of drug candidate fail in clinical trials, meaning that the selection of molecules during preclinical steps is not relevant enough. High Content Screening (HCS) has been an important breakthrough in drug discovery by analyzing no more one specific target but the full cell phenotype, and thus by considering all the complex pathological involved in multifactorial diseases like cancers. However, HCS potential is still limited by the current in vitro models, which don’t reproduce all the complexity of cancer by missing the microenvironment of the cancerous cells, in particular the Extracellular Matrix (ECM). Indeed, more and more studies demonstrate that both the composition and the stiffness of the ECM are modified in tumors and are strongly linked to cancer initiation, progression, and propagation, as well as in drug resistance. That’s why we propose to include the matrix in HCS models, for a more relevant first step of drug selection.
In this purpose, we developed BIOMIMESYS®, a hyaluronic acid-based matrix bio-functionalized with structural and adhesion molecules of the native ECM, which forms a relevant microenvironment for in vitro 3-dimensional cell culture. This ECM-like hydroscaffold™ combines both the advantages of solid scaffold (porosity and structure maintenance) and of hydrogels (cell-matrix interactions), thus close to decellularized tissues. Its composition, porosity and stiffness can be modified to reproduce the tissue-specificity of the native ECM, or to mimic a pathological microenvironment like the tumoral ECM. This matrix is chemically defined, translucent and provided ready-to-use in multi-well plate format (96- and 384-well plates). It can therefore be used for High Content Screening. We develop several 3D models for phenotypic screening in oncology, including colon, lung, liver and breast cancer.
We have demonstrated by phenotypic analysis that BIOMIMESYS® Oncology matrix offers better correlations with in vivo data than 2D models. Our results showed that the matricial microenvironment modifies the behavior of cancerous cells in vitro and should be considered carefully in drug discovery. Phenotypic screening using BIOMIMESYS® hydroscaffold™ offers results predictive to clinical outcomes.
She looking forward to meet you to discuss with you about ECM, 3D models and High Content Screening!
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