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Abstract: In oncology, 97% of drug candidates fail in clinical trials. This highlights a lack of relevance of preclinical models used upstream. Indeed, human in vitro models don’t consider the Tumoral Extracellular Matrix (TECM). However, more and more studies demonstrate that ECM composition and stiffness are modified in tumors and are linked to cancer initiation, progression, propagation, and drug resistances.
BIOMIMESYS® is a Hyaluronic Acid-based matrix grafted with structural and adhesion molecules, which mimics the ECM/TECM. It is chemically defined and its composition and stiffness can be modified to reproduce the organ-specificity of the ECM, or to mimic a pathological microenvironment in vitro.
We have demonstrated that the exposition of colon cancer cells cultured in BIOMIMESYS® Oncology matrix to an anti-proliferative drug showed a closer in vitro/in vivo correlation in the EC50 curve compared to 2D culture. Cancer cells can be advantageously grown in BIOMIMESYS® for several weeks in multiwell plates and in microfluidic chips for more advanced models. We also observed that modifications in the matrix composition and stiffness modify the cell behavior. Moreover, thanks to collaborations with academic laboratories, we demonstrated that BIOMIMESYS® allows to reproduce in vitro the behavior of cancerous cells in vivo, like mutation effects and metastasis propagation, and could be a relevant alternative to animal models. These results showed that the matricial microenvironment modifies the cell behavior in vitro and should be considered carefully in drug discovery. BIOMIMESYS® hydroscaffold™ is adapted to High Content Screening and represented a powerful tool to better select drug candidate.