Treatment Associated Escalation in p Akt is Not Associated with Everolimus Resistance in Patients Recently, everolimus has been proven to increase progression free survival of pancreatic neuroendocrine tumors and Bortezomib structure has received FDA approval. For that reason, we decided whether Akt activation correlated with PFS on everolimus based therapy. Archival cyst blocks were accessible on 23 patients treated on the Phase II trial of octreotide and everolimus. All cancers expressed p mTOR and almost all expressed PTEN. There have been no major differences in PFS based on expression of p Akt S473, p 4E BP1 T37/46 or p S6 S235/236 on archival samples. Pre treatment and on treatment fine needle aspirations were obtained in 17 patients on the trial after informed consent, as biomarker investigation on the tumor being treated may be more clinically relevant than biomarkers on archival tissue. Pre treatment and on treatment useful proteomics on FNAs samples were assessed by RPPA. We determined whether g Akt levels Lymphatic system on RPPA were related to PFS. We found that large p Akt T308 levels on treatment FNAs in addition to on baseline pre treatment FNAs correlated with longer PFS. On RPPA, we demonstrated that S6 phosphorylation was certainly significantly decreased on p S6 235/236 and p S6 S240/244, demonstrating inhibition of mTOR signaling. As RS cell lines were more prone to have feedback cycle service than RR cell lines, we examined the effect of everolimus on g Akt T308 levels. Patients who’d a partial response with everolimus therapy were much more likely to have escalation in r Akt T308 than patients who had stable illness or progression. Five patients had coupled pre treatment and one of these patients had activation of Akt signaling, and had a partial answer, on treatment core biopsies with IHC evaluable for p Akt S473. Debate Rapamycin analogs have been ALK inhibitor subependymal giant cell astrocytoma associated with tuberous sclerosis, FDA-APPROVED for treating renal cell carcinoma, and pancreatic neuroendocrine tumors, and have demonstrated promising antitumor efficacy in other cancer types. Nevertheless, rapalogs demonstrate objective responses in mere a subset of patients. Identification of predictors and pharmacodynamic guns of rapamycin response can help select patients most likely to take advantage of rapalogs, and assess response early in the procedure program, and establish components of therapy resistance that can be targeted for combinatorial therapy. Our goal was to determine whether PI3K route mutations/ initial i. Elizabeth. rapamycin induced feedback loop activation of Akt is connected with rapamycin sensitivity or resistance. We demonstrated that cell lines with PIK3CA or PTEN mutations were prone to be RS.