Pancreatic cancer is one of the most aggressive malignancies with only 5% of patients being alive 5 years after diagnosis. Tumor microenvironment is certainly involved in the progression of pancreatic carcinoma through subsequent steps of metastatic dissemination. Thus, both angiogenesis and epithelial-to-mesenchymal transition (EMT) are essential results of cancer-stroma interaction.
Both endoscopic ultrasound (EUS) and confocal laser endomicroscopy (CLE) are recent techniques that could be used to evaluate imaging surrogate biomarkers used for a tailored personalised therapy in these patients. Recently, CLE has gone beyond the superficial luminal indications with the development of a new microprobe, i.e. a flexible probe that can pass through a 19-gauge needle (nCLE).
The aim of the current project is focused on the evaluation of both angiogenic factors and characterization of the EMT status, which have proven to exhibit variable prognostic values in pancreatic cancer. This hypothesis is endorsed by recently published data showing that TGFbeta can induce EMT as a pro-oncogenic event, whilst this might be also promoted by VEGF-induced autocrine loops.
The specific objectives of the proposal include:
O1 Real-time translational hybrid imaging methods used for the evaluation of pancreatic carcinoma, especially for the prognostic assessment based on molecular imaging biomarkers.
O2 Reverse-translational evaluation of angiogenesis and EMT, validated by immunohistochemistry (IHC), immune-fluorescence (IF) and molecular biology techniques (qPCR, microarray).
The method of EUS-guided nCLE is novel and studies on how to improve the technique using different targeted markers are highly relevant. If nCLE could be used for real-time characterization of the molecular profile of pancreatic carcinomas this could evolve into a whole new area of research ultimately leading to individualized oncological treatment.