SMAD3 and central nervous system cancer: Even though SMAD3 inhibition might reduce cell viability of certain GB subtypes63, our data underlines the importance of the cellular context, i.e., contacts with neurons, where the combination of neural activity stimulation and SMAD3 inhibition have proven to additively cooperate to promote proliferation of GB cells (Fig. 8b), both in co-culture systems that model neuron-to-glioma interactions and in PDX models in mice.