Modelling the microenvironment of the most aggressive brain tumours for preclinical studies

Abstract

Preclinical and clinical cancer studies use unrepresentative tumour models that do not properly simulate the intricate pathobiology of the human tumour and its complex microenvironment. This is of critical importance for the brain tumour glioblastoma (GBM), one of the most malignant cancers, which almost always relapses despite treatment. Due to the intertumoral and intratumoral heterogeneity of GBM, it is highly resistant to conventional treatment with radiotherapy and chemotherapy. In this review, we describe the heterogeneity of GBM and the unique microenvironment of brain tumours as well as their importance for GBM progression and to set up clinically relevant GBM models for successful preclinical research and drug screening. A combination of cancer cells, cancer stem cells, and cancer-associated cells create an intricate and diverse tumour microenvironment. GBM is very adept at recruiting healthy cells to support itself. The function of these cancer-associated cells varies in different niches, but they all share the common function of promoting tumour growth and spread. Glioblastoma stem cells are one of the central components of GBM treatment resistance, invasiveness, and cancer stem cell niche relationships. All of these aspects are critical when selecting and designing preclinical GBM models.