Abstract

In oncology, 97% of drug candidates fail in
clinical trials, pointing a lack of relevance of preclinical models. Indeed, human
in vitro models don’t take into
account the microenvironment, in particular the Extracellular Matrix (ECM), although it is modified in tumors and strongly
linked to cancer initiation, progression, propagation, and drug resistance.

BIOMIMESYS® is a hyaluronic acid-based matrix bio-functionalized with structural and
adhesion molecules of ECM, providing a relevant microenvironment for in vitro 3D cell culture. This ECM-like hydroscaffold
combines the advantages of solid scaffolds (porosity, structure) and hydrogels
(cell-matrix interactions). It is chemically defined and ready-to-used in
multi-well plates, thus it can be used for High Content Screening (HCS).
Moreover, its composition and stiffness can be modified to reproduce the
organ-specificity of the ECM, or to mimic a pathological microenvironment like
in cancer.

Cancer cells can be advantageously grown in BIOMIMESYS® for several
weeks. The EC50 curve of cancer cells exposed to an
anti-cancerous drug showed a closer in
vitro/in vivo correlation in BIOMIMESYS® than in 2D. We also demonstrated that BIOMIMESYS® allows to reproduce in vitro the behavior of cancerous cells in
vivo, like mutation effects and metastasis propagation. These results
showed that the matricial microenvironment modifies the behavior of cancerous
cells in vitro and should be considered
carefully in drug discovery. This hydroscaffold offers a good predictability
and is adapted to HCS; it represents a powerful tool to better select drug
candidates and to increase the success rate in clinical trials.