Brain Tumor Networks in Diffuse Glioma

Diffuse gliomas are primary brain tumors associated with a poor prognosis. Cellular and molecular mechanisms driving the invasive growth patterns and therapeutic resistance are incompletely understood. The emerging field of cancer neuroscience offers a novel approach to study these brain tumors in the context of their intricate interactions with the nervous system employing and combining methodological toolsets from neuroscience and oncology. Increasing evidence has shown how neurodevelopmental and neuronal-like mechanisms are hijacked leading to the discovery of multicellular brain tumor networks. Here, we review how gap junction-coupled tumor-tumor-astrocyte networks, as well as synaptic and paracrine neuron-tumor networks drive glioma progression. Molecular mechanisms of these malignant, homo- and heterotypic networks, and their complex interplay are reviewed. Lastly, potential clinical-translational implications and resulting therapeutic strategies are discussed. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13311-022-01320-w.