Truly future clinical trials designed to try the result of this biomarker is going to be important to determine whether FKBP5 can be used as a biomarker for the selection of treatment for individual patients. As well as the function of FKBP5 in chemoresistance, according to our xenograft models it may also Cabozantinib clinical trial work as a tumor suppressor through bad regulation of the Akt pathway. As shown in Figures 3 and 5A, exercise of the Akt pathway is notably higher in FKBP5 knock-down SU86 xenografts than that in wild type SU86 xenografts and these findings correlated with higher tumefaction growth rates in mice. For that reason, probably due to the higher basal levels of Akt exercise, shFKBP5 xenografts responded better to combination treatment, that was viewed as increased inhibition of tumefaction growth. This phenomenon was also reflected by reduced Akt 473 phosphorylation levels after TCN and gemcitabine treatment. The shFKBP5 xenografts showed a more dramatic reduction in Akt 473 phosphorylation levels wt xenografts. Our in vivo results further confirmed results observed using the cell lines. These studies demonstrated that insufficient expression of FKBP5 resulted in increased Akt phosphorylation at the regulatory S473 amino-acid residue as well as for downstream genes within the Akt pathway such as phosphorylated FOXO1 and GSK3b. For that reason, FKBP5 could be described as a tumor Resonance (chemistry) suppressor in pancreatic cancer and it could also be a biomarker for response to chemotherapy, especially gemcitabine treatment, a first line treatment for pancreatic cancer. Our findings that resistance can be reversed by a specific Akt inhibitor to gemcitabine in FKBP5 knock-down cells and xenografts show that FKBP5 levels could be used to stratify patients into different treatment arms, such as gemcitabine or gemcitabine plus an Akt inhibitor. Future clinical studies is going to be required to try this hypothesis. Moreover, the mechanisms underlying differences between the results of mTOR inhibition, PI3K inhibition and Akt inhibition in conjunction with JZL184 1101854-58-3 gemcitabine have to be explored further. PI3K service causes phosphatidylinositol 3,4,5 triphosphate dependent membrane localization of Akt and PDK1, where the latter can phosphorylate Akt 308. For that reason, the inhibition of PI3K could have less influence on 473 phosphorylation. Rapamycin could possibly activate Akt 473 phosphorylation within an mTOR 2 dependent method on account of reduction of feedback inhibition of IGF 1R signaling. Which could explain why treatment with rapamycin plus gemcitabine did not show an important reduction of Akt 473 phosphorylation. Certainly, these findings need to be verified by additional studies using human trials or transgenic mice. However, currently it’s challenging to obtain sufficient clinical samples with similar clinical features treated with gemcitabine alone to determine the relationship between treatment and FKBP5 response since most patients are treated with multiple agents.