Figure 2.

Effect of combined somatostatin analog and mammalian target of rapamycin (mTOR) inhibitor therapy in neuroendocrine tumors. Combined treatment with an mTOR inhibitor and a somatostatin analog has been shown to cause tumor cell cycle arrest in vitro [57]. The indirect inhibition of mTOR through phosphoinositase-3-kinase/Akt resulting from the somatostatin analog seems to increase sensitivity to mTOR inhibition.

Abbreviations: cAMP, cyclic adenosine monophosphate; cGMP, cyclic guanosine monophosphate; HIF, hypoxia-inducible factor; IGF, insulin-like growth factor; IGF-1R, insulin-like growth factor receptor 1, MAPK, mitogen-activated protein kinase; mTOR, mammalian target of rapamycin; NET, neuroendocrine tumor; NF1, nuclear factor 1; NFκB, nuclear factor-κB; PI3K, phosphoinositase-3-kinase; PTEN, phosphatase and tensin homolog; SHP1, Src homology phosphatase-1; sst, somatostatin; TSC, tuberous sclerosis complex; VEGF, vascular endothelial growth factor; VEGFR, vascular endothelial growth factor receptor; VHL, Von Hippel-Lindau.