Fig. 1: Challenges to curing primary brain tumours at different stages of tumour development.

The nonmalignant cellular composition of the ventricular–subventricular zone includes neural stem cells that divide and produce transit-amplifying cells. Transit-amplifying cells give rise to migratory neuroblasts⁹⁰. Ependymal cells are also present in the neural stem cell niche. The niche is intimately associated with blood vessels and might also communicate with other cell types, including microglia and astrocytes. Malignant transformation of neural stem cells presumably leads to the premalignant expansion of transit-amplifying cells and migratory neuroblasts as the nonmalignant hierarchy begins to transform. This unregulated hierarchy generates the malignant brain tumour. As these lesions are treated, tumour cells are killed, with the ultimate goal of eventual cure. The blue panels below these cartoons denote the focus of key research questions at each stage, from nonmalignant brain tissue to the development of cancer and remission following successful treatment. The green panels depict how the seven challenges to progress relate to these specific stages of disease development.