Multimodal Assessment of Dynamic Biological Behavior of Pancreatic Cancer-DYOPAC
Ref. No. 101TE dated 03/01/2025
Project Manager: Ungureanu Bogdan
Time: 03/01/2025-31/12/2026
The DYOPAC project embraces the path of uncovering specific imaging and biological markers for the dynamic behavior of pancreatic cancer (PC) by using state-of-the-art procedures. The endeavor of combining Endoscopic Ultrasound techniques and Confocal Endomicroscopy as non-invasive methods of Cancer-Associated Fibroblasts (CAFs) may provide a more rapid and efficient predictive response to therapeutic management. A multimodality characterization of CAFs would be useful in PDAC disease upgrading and response to novel therapies. The current project proposal provides several unique features for PDAC assessment. Firstly, it provides a longitudinal evaluation of PDAC patients by including Dynamic Contrast Enhanced-EUS, and Elastography-EUS with specific software denominators directly compared with immunohistochemistry biomarkers to predict tumor evolution. Secondly, reverse-translational molecular assessment of the tumor microenvironment CAFs by targeted imaging along with IHC and molecular biology techniques will provide new clinical models and an understanding on how disease evolves. The final objective will be to develop a specific framework for tumor dynamic biologic behavior which will consist of different biomarkers to have a better prediction of PDAC prognosis and response to therapy.
Our Team:
Bogdan Silviu Ungureanu – Project Manager
Lucian Mihai Florescu – Postdoctoral Research Fellow
Adina Turcu-Știolica – Research Fellow
Cristian Lungulescu – Postdoctoral Research Fellow
Mirela Marinela Florescu – Postdoctoral Research Fellow
Oana Iulia Crețu – Postdoctoral Research Fellow
STAGES AND ACTIVITIES
Stage 1 – Non-invasive dynamic analysis of the PDAC stroma at diagnosis and three months after treatment initiation, using imaging biomarkers for vascular behavior and stiffness (DCE-EUS, EUS-EG, MRI-DWI, DCE-MRI), and initiating the evaluation of cancer-associated fibroblasts (CAFs), with direct correlation to progression-free survival and overall survival in PDAC patients.
Act.1.1 – Development of a structured database, clinical protocols, and ethical approvals
Act.1.2 – Longitudinal evaluation using multimodal imaging (EUS) and DCE-MRI parameters in PDAC patients
Act.1.3 – EUS-guided FNB for diagnosis and IHC testing
Act.1.4 – Initiation of CAF evaluation on FNB-EUS tumor samples
Act.1.5 – Initiation of prognostic evaluation of CAF expression
Stage 2 – Continuation of CAF evaluation and correlation with progression-free and overall survival, reverse-translational CAF imaging validation using immunohistochemistry and molecular biology techniques (qPCR, microarray), and development of an integrated platform for predicting the dynamic behavior of the PDAC stroma in clinical survival analysis, based on prognostic stratification including imaging and pathological variables.
Act.2.1 – Continued longitudinal multimodal imaging (EUS) and DCE-MRI assessment for PDAC patients
Act.2.2 – Prognostic value calculation of perfusion and stiffness imaging parameters from Act.2.1
Act.2.3 – Continued evaluation of CAFs and correlation with survival outcomes
Act.2.4 – Ongoing CAF assessment on EUS-FNB tumor samples
Act.2.5 – Prognostic evaluation of CAF expression (similar to Act.2.2)
Act.2.6 – Morphometric CLE assessment of EUS-FNB specimens
Act.2.7 – Ex vivo molecular CLE (mCLE) based on CAF markers
Act.2.8 – Development of a predictive framework for the biological behavior of the PDAC stroma