Abstract
Glioblastoma (GBM) is a devastating adult brain cancer with high rates of recurrence and treatment resistance. Cellular heterogeneity and extensive invasion of surrounding brain tissues are characteristic features of GBM that contribute to its intractability. Current GBM model systems do not recapitulate some of the complex features of GBM and have not produced sufficiently-effective treatments. This has cast doubt on the effectiveness of current GBM models and drug discovery paradigms. In search of alternative pre-clinical GBM models, various 3D organoid-based GBM model systems have been developed using human cells. The scalability of these systems and potential to more accurately model characteristic features of GBM, provide promising new avenues for pre-clinical GBM research and drug discovery efforts. Here, we review the current suite of organoid-GBM models, their individual strengths and weaknesses, and discuss their future applications with an emphasis on compound screening.
Highlights
Glioblastoma (GBM) is a devastating adult brain cancer with high rates of recurrence and treatment resistance
Multiple observations support the hydrodynamic invasion model: (1) time-lapse imaging shows that invading GBM cells undergo dramatic morphology and volume changes (Watkins and Sontheimer, 2011), (2) invasiveness correlates with the expression of ion transporters that drive water exchange in GBM (Garzon-Muvdi et al, 2012), and (3) genetic or pharmacological inhibition of these ion channels reduces GBM infiltration (Soroceanu et al, 1999; Haas and Sontheimer, 2010; Lui et al, 2010; Garzon-Muvdi et al, 2012)
We review the recent progress that has been made to develop novel human-specific organoidGBM model systems that may help to overcome some of these limitations
Summary
Cellular heterogeneity and extensive invasion of surrounding brain tissues are characteristic features of GBM that contribute to its intractability. Current GBM model systems do not recapitulate some of the complex features of GBM and have not produced sufficiently-effective treatments. This has cast doubt on the effectiveness of current GBM models and drug discovery paradigms. In search of alternative pre-clinical GBM models, various 3D organoid-based GBM model systems have been developed using human cells. The scalability of these systems and potential to more accurately model characteristic features of GBM, provide promising new avenues for pre-clinical GBM research and drug discovery efforts.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
