In vitro models of the interplay between glioblastoma and blood-brain barrier for stratifying drug efficacy

Area of Science:

• Neuro-oncology
• Biomedical Engineering
• Drug Delivery Systems

Background:

• Glioblastoma (GBM) is a fatal brain cancer with limited treatment options due to the blood-brain barrier (BBB) hindering drug penetration.
• Current therapies like temozolomide (TMZ) and radiotherapy show limited efficacy, with over 98% of drug candidates failing to cross the BBB.
• Existing preclinical models inadequately represent the complex BBB-GBM interaction, necessitating improved research platforms.

Purpose of the Study:

• To review recent advancements in in vitro models designed to mimic the BBB-GBM interplay.
• To highlight innovative models that enhance the physiological relevance and predictive value for anti-GBM drug testing.
• To emphasize the need for models that support the 3Rs principles (replacement, reduction, refinement) in research.

Main Methods:

• Discussion of various in vitro model advancements, from 2D systems to 3D constructs.
• Highlighting innovations like microfluidic devices and multicellular spheroid cultures.
• Focusing on models that replicate the BBB and GBM microenvironment interaction.

Main Results:

• Advanced in vitro models offer more accurate replication of the BBB-GBM interface compared to traditional methods.
• Microfluidic and spheroid models show promise for enhancing the physiological relevance of drug testing.
• These models aim to accelerate the discovery and efficacy evaluation of novel GBM therapeutics.

Conclusions:

• There is a critical need for more representative in vitro models to overcome BBB limitations in GBM drug delivery.
• Improved models can reduce reliance on animal testing and adhere to the 3Rs principles.
• These advancements are essential for developing more effective therapeutic strategies against GBM.