We have recently showed that the immunophilin FKBP5 (also known as FKBP5) as a scaffolding protein that can enhance PHLPP-AKT interaction and facilitate PHLPP-mediated dephosphorylation of AKT-Ser473, negatively regulating AKT activation in vitro. Therefore, FKBP5 might function as a tumor suppressor and levels of FKBP5 would affect cell response to chemotherapy. In the current study, we took a step forward by using pancreatic caner xenograft mice model to show that FKBP5−/− promotes tumor growth and renders resistance to gemcitabine and addition of AKT inhibitors have more significant sensitization effect on FKBP5−/− mice to gemcitabine treatment. The combination of triciribine and gemcitabine resulted in cooperative inhibition of pancreatic cancer cell proliferation and the growth of xenografts in vivo without increasing toxicity, as well as cooperative inhibition of AKT signaling pathways at concentrations that were ineffective as individual agents. These results provide evidence for future clinical studies designed to tailor the therapy based on the biomarker.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr C15.