Engineering Advanced Models of the Glioblastoma Microenvironment Using Biomaterials
Glioblastoma (GBM) is the most common and deadly primary brain cancer. Patients diagnosed with GBM have a mean survival time of only 21 months, despite an intense push over the past several decades to dissect underlying mechanisms and develop new therapies. Whereas discovery efforts related to GBM have traditionally focused on cell-intrinsic factors, such as genetic and epigenetic lesions, it has more recently become clear that cell-extrinsic factors within the tumor microenvironment play important pathogenic roles as well. More surprisingly, physical aspects of the microenvironment, including tissue structure and mechanics, can regulate signaling events that contribute to dysplasia, invasion, and metastasis. This chapter will describe the basic biology of physical microenvironmental regulation of the GBM, with a focus on the extracellular matrix. We will also describe how components of the physical microenvironment can be recapitulated using biomaterials technology and how these new platforms can contribute to next-generation culture systems for discovery and screening.
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