Central nervous system tumors and three-dimensional cell biology: Current and future perspectives in modeling

Central nervous system (CNS) tumors are a variety of distinct neoplasms that present multiple challenges in terms of treatment and prognosis. Glioblastoma, the most common primary tumor in adults, is associated with poor survival and remains one of the least treatable neoplasms. These tumors are highly heterogenous and complex in their nature. Due to this complexity, traditional cell culturing techniques and methods do not provide an ideal recapitulating model for the study of these tumors’ behavior in vivo. Two-dimensional models lack the spatial arrangement, the heterogeneity in cell types, and the microenvironment that play a large role in tumor cell behavior and response to treatment. Recently, scientists have turned towards three-dimensional culturing methods, namely spheroids and organoids, as they have been shown to recapitulate tumors in a more faithful manner to their in vivo counterparts. Moreover, tumor-on-a-chip systems have lately been employed in CNS tumor modeling and have shown great potential in both studying the pathophysiology and therapeutic testing. In this review, we will discuss the current available literature on in vitro three-dimensional culturing models in CNS tumors, in addition to presenting their advantages and current limitations. We will also elaborate on the future implications of these models and their benefit in the clinical setting.