Cell-Based Glioma Models for Anticancer Drug Screening: From Conventional Adherent Cell Cultures to Tumor-Specific Three-Dimensional Constructs

Abstract

Gliomas are a group of primary brain tumors characterized by their aggressive nature and resistance to treatment. Infiltration of surrounding normal tissues limits surgical approaches, wide inter- and intratumor heterogeneity hinders the development of universal therapeutics, and the presence of the blood-brain barrier reduces the efficiency of their delivery. As a result, patients diagnosed with gliomas often face a poor prognosis and low survival rates. The spectrum of anti-glioma drugs used in clinical practice is quite narrow. Alkylating agents are often used as first-line therapy, but their effectiveness varies depending on the molecular subtypes of gliomas. This highlights the need for new, more effective therapeutic approaches. Standard drug-screening methods involve the use of two-dimensional cell cultures. However, these models cannot fully replicate the conditions present in real tumors, making it difficult to extrapolate the results to humans. We describe the advantages and disadvantages of existing glioma cell-based models designed to improve the situation and build future prospects to make drug discovery comprehensive and more effective for each patient according to personalized therapy paradigms.

Keywords: brain tumors; cancer; cell-based screening; early passage cells; genetically modified model; glioma; organoid; patient-derived culture; spheroid; three-dimensional model.

Figure 1

Key molecular pathways, onco-associated molecules, and the microenvironment involved in gliomagenesis as prospective targets for glioma therapy that should be modeled in vitro.

Figure 2

Application of the patient-derived glioma cell-based models.

Figure 3

Approaches employed to create genetically modified glioma cell-based models and their subsequent applications. The left section shows the cell types most frequently utilized for modification, while the right section illustrates the various genetic and epigenetic modifications.

Figure 4

Approaches for creating 3D cell-based glioma models. The left side of the figure shows the main cell sources for scaffold-free and scaffold-based models, while the right side shows the scaffold options for scaffold-based models.