Limitations in small intestinal neuroendocrine tumor therapy by mTor kinase inhibition reflect growth factor–mediated PI3K feedback loop activation via ERK1/2 and AKT

Abstract

SINET treatment with the mTOR inhibitor RAD had no antiproliferative effect based on activation of pAKT and pERK1/2. A combinatorial approach using OCT and RAD failed to overcome this escape phenomenon. However, differences in RAD response rates in individual NET cell lines suggested that pretreatment identification of different tumor sensitivity to mTOR inhibitors could provide the basis for individualized treatment.