IGF1 and neuroblastoma: In addition, activation of the PI3K/Akt/mTOR pathway by growth factors, including insulin-like growth factor (IGF)-1, was reported to lead to mTOR phosphorylation, increased HIF-1α expression, and to induce HIF-1α-mediated VEGF transcription and secretion in distinct NB cell lines [48], which were blocked by mTOR or PI3K inhibition using specific small-molecule inhibitors [49], suggesting that targeting the PI3K/Akt/mTOR pathway has the potential to inhibit VEGF expression and limit NB tumor growth by inhibiting HIF-1 expression and activity.