Advances in 3D culture systems for therapeutic discovery and development in brain cancer.

• Existing models for drug discovery and development against glioblastoma multiforme (GBM) have limitations. • We review advances in 3D systems that promise more accurate therapeutic models. • Development of 3D cultures that can model the GBM tumor microenvironment is discussed. • We describe advanced 3D systems such as organoids, 3D and 4D bioprinting, and cancer stem cells. • We identify gaps to bridge in existing 3D systems to accelerate drug discovery. This review focuses on recent advances in 3D culture systems that promise more accurate therapeutic models of the glioblastoma multiforme (GBM) tumor microenvironment (TME), such as the unique anatomical, cellular, and molecular features evident in human GBM. The key components of a GBM TME are outlined, including microbiomes, vasculature, extracellular matrix (ECM), infiltrating parenchymal and peripheral immune cells and molecules, and chemical gradients. 3D culture systems are evaluated against 2D culture systems and in vivo animal models. The main 3D culture techniques available are compared, with an emphasis on identifying key gaps in knowledge for the development of suitable platforms to accurately model the intricate components of the GBM TME. [ABSTRACT FROM AUTHOR]