mTOR signaling can be a promising target in neuroendocrine tumors. Within our Phase II trial of everolimus and octreotide LAR in advanced level low and intermediate grade neuroendocrine tumors, intention to take care of response rate was 20%. Eventually everolimus alone was proven to have anti-tumor purchase Canagliflozin efficacy in a Phase II trial of everyday oral everolimus in patients with metastatic pancreatic neuroendocrine tumors after failure of cytotoxic chemotherapy. Lately, a Phase III trial, everolimus was shown to considerably improve progression free survival when compared with placebo. These information recently generated the FDA approval of everolimus for pancreatic neuroendocrine tumors. Nevertheless, even in this registration trial, objective partial responses were observed in only five minutes of patients receiving everolimus. Ergo, the power from everolimus regarding progression free survival was seen primarily in infection stabilization or slight cyst shrinkage. Thus it may be of great value to identify biomarkers that can up-front predict which patients with neuroendocrine Papillary thyroid cancer tumors may derive the maximum clinical benefit. Recently, large through set characterization of pancreatic neuroendocrine tumors has identified variety genomic aberrations including repeated aberrations DAXX, ATRX, TSC2, MEN1, PTEN, and PIK3CA. Studies are ongoing to determine the position of those genomic aberrations in rapalog sensitivity. As expected, we demonstrated that cell lines with PTEN mutations had increased Akt phosphorylation. There is no agreement on whether PIK3CA versions trigger PI3K signaling. PIK3CA strains were reported to be related to increased p Akt levels Fostamatinib Syk inhibitor in pancreascancer examples and in selected breast cancer cell lines, while others have found no obvious association. Our data supports an escalation in Akt phosphorylation in PIK3CA mutant cell lines. However, the g Akt height seen with PIK3CA mutations is not as powerful as that observed with PTEN mutations. More, we didn’t analyze the differences in downstream signaling by genotype. In vitro standard large g Akt levels are associated with rapamycin sensitivity. That is in keeping with previous reports. Nevertheless, despite intense study of PI3K/mTOR signaling in cancer biology, presently there are no validated assays to evaluate Akt phosphorylation or pathway activation in the center. Within our Phase II study, p Akt levels on archival tissue were not associated with outcome, while p Akt levels on FNAs related with PFS. This could be a reflection of tumefaction evolution with time, or difficulties with IHC with phospho specific antibodies on archival samples. Consistent with this, we’ve previously demonstrated that there is an important discordance when IHC for p Akt and p 4E BP1 in primary breast cancers were compared to these in matched distant metastases.