Depiction of a p53-deficient OCSCC tumor releasing EVs onto nearby trigeminal sensory neuron. These EVs carry pro-neuritogenic miRNAs, including miR-21 and miR-324. Along with driving neuritogenesis, these miRNAs also drive a sensory-to-sympathetic transition in these neurons. Sympathetic innervation of tumors and tumor microenvironments drives growth and spread of the tumor. Sympathetic release (adrenaline, noradrenaline) directly stimulates growth in certain tumors. In addition, sympathetic release stimulates endoneurial macrophages, which facilitate tumor growth and angiogenesis. In concert, sympathetic release stimulates ADRĪ²2 receptors, thereby driving a glycolytic switch in endothelial cells to spur angiogenesis.