Extracellular matrix in glioblastoma: opportunities for emerging therapeutic approaches

Extracellular matrix is a complex network of macromolecules that constitute a microenvironment of normal tissues and malignancies such as the primary brain tumor glioblastoma (GBM). The unique composition of the GBM ECM, compared with the brain, contributes to angiogenesis, invasion, and therapeutic resistance of GBM. On the other hand, components of tumor ECM and related aberrant signaling pathways offer opportunities for various therapeutic strategies that are under active investigations. Here we provide a comprehensive overview of emerging therapeutic approaches for GBM that target or utilize its unique ECM via antibodies or ligands, RNA interference, pharmacological agents and modification of ECM molecules. Furthermore, drug-loaded nanoparticles displaying ECM-directed antibodies or peptides enable tumor selective delivery of the payload. As an in vitro research platform, 3D tumor cell culture incorporating ECM can advance our understanding of tumor-ECM interactions.