From cells to organoids: The evolution of blood-brain barrier technology for modelling drug delivery in brain cancer

Brain cancer remains the deadliest cancer. The blood–brain barrier (BBB) is impenetrable to most drugs and is a complex 3D network of multiple cell types including endothelial cells, astrocytes, and pericytes. In brain cancers, the BBB becomes disrupted during tumor progression and forms the blood–brain tumor barrier (BBTB). To advance therapeutic development, there is a critical need for physiologically relevant BBB in vitro models. 3D cell systems are emerging as valuable preclinical models to accelerate discoveries for diseases. Given the versatility and capability of 3D cell models, their potential for modelling the BBB and BBTB is reviewed. Technological advances of BBB models and challenges of in vitro modelling the BBTB, and application of these models as tools for assessing therapeutics and nano drug delivery, are discussed. Quantitative, in vitro BBB models that are predictive of effective brain cancer therapies will be invaluable for accelerating advancing new treatments to the clinic.