Targeting PI3K/mTOR signaling displays potent antitumor efficacy against nonfunctioning pituitary adenomas

摘要: Purpose: Novel therapeutic approaches are needed to improve the postoperative management of residual nonfunctioning pituitary adenomas (NFPA), given their high relapse rate. Here, we evaluated antitumor efficacy dual PI3K/mTOR inhibitor NVP-BEZ235 in only available model spontaneous NFPAs (MENX rats). Experimental Design: Organotypic cultures rat primary were incubated with and assessed for cell viability, proliferation, apoptosis, inhibition. NVP-BEZ235, or placebo, was administered MENX rats tumor response monitored noninvasively by diffusion weighted-magnetic resonance imaging (DW-MRI). Following treatment, tissues investigated Genes mediating cytotoxic activity identified gene-expression profiling. Among them, Defb1 , encoding beta-defensin 1, further studied its role cells human pancreatic neuroendocrine (NET) cells. Results: showed antiproliferative pro-cell death activities against both vitro vivo drug correlated inhibition PI3K pathway. DW-MRI early functional changes (decreased cellularity) before size affected emerged as a useful modality assess therapy response. The effect blockade NFPA mediated several genes, including . treatment induced expression NET High levels sensitized Conclusions: Our findings provide rationale clinical investigation identify novel effectors PI3K-mediated survival. Clin Cancer Res; 21(14); 3204–15. ©2015 AACR