Therapy Associated Escalation in p Akt isn’t Associated with Everolimus Resistance in Patients Recently, everolimus has demonstrated an ability to extend progression free survival of pancreatic neuroendocrine tumors and Avagacestat 1146699-66-2 has received FDA approval. Thus, we determined whether Akt activation correlated with PFS on everolimus based treatment. Archival tumefaction blocks were available on 23 patients treated on the Phase II trial of everolimus and octreotide. All tumors expressed p mTOR and nearly all expressed PTEN. There were no major differences in PFS based on expression of p Akt S473, p 4E BP1 T37/46 or p S6 S235/236 on samples. As biomarker research on the cyst being treated could be more clinically relevant than biomarkers on archival tissue, pre treatment and on treatment fine needle aspirations were obtained in 17 patients on the trial after informed consent. On and pre treatment treatment useful proteomics on FNAs products were examined by RPPA. We determined whether p Akt levels Metastasis on RPPA were connected with PFS. We discovered that high p Akt T308 levels on baseline pre treatment FNAs as well as on treatment FNAs correlated with longer PFS. On RPPA, we demonstrated that S6 phosphorylation was certainly significantly decreased on p S6 S240/244 and p S6 235/236, demonstrating inhibition of mTOR signaling. We examined the effect of everolimus on r Akt T308 degrees, As RS cell lines were more prone to have feedback trap activation than RR cell lines. Patients who had a partial response with everolimus therapy were a lot more likely to have an escalation in p Akt T308 than patients who had stable disease or progression. Five patients had used pre treatment and among these patients had activation of Akt signaling, and had a partial answer, on treatment core biopsies with IHC evaluable for p Akt S473. Conversation Rapamycin analogs have been Hedgehog inhibitor subependymal giant cell astrocytoma associated with tuberous sclerosis, FDA approved for treating renal cell carcinoma, and pancreatic neuroendocrine tumors, and have shown promising antitumor efficacy in other cancer types. However, rapalogs have shown objective responses in mere a subset of patients. Identification of predictors and pharmacodynamic prints of rapamycin response can help select patients most likely to take advantage of rapalogs, and evaluate response early in the treatment course, and identify components of therapy resistance that can be qualified for combinatorial therapy. Our goal was to ascertain whether PI3K route mutations/ service i. e. rapamycin induced feedback loop activation of Akt is related to rapamycin sensitivity or resistance. We demonstrated that cell lines with PIK3CA or PTEN mutations were more likely to be RS.