Innovative Therapeutic Treatments to Inhibit Perineural Invasion in Pancreatic Adenocarcinoma

STUDY DESIGN The overarching goal of this project is to develop new therapeutic approaches to limit PNI formation and therefore PDAC formation and metastasis. PNI, has its higher incidence in PDAC, in which it is a recognized risk factor of poor survival. Considering the clinical relevance of PNI and its role in PDAC, it is urgent to identify molecular PNI signatures to develop new therapeutic strategies. We have recently identified a molecule (FGFBP1) that is activated in pancreatic cancer cells and initiate PNI.

This project is designed as an observational multicentric, cross-sectional study. OSR is the only center enrolling patients. OSR will send organoids derived from biological samples of enrolled patients to the participating center UO 3 (ASL3 Lecce) that will perform proteomic analyses to determine the level of expression of FGFBP1 inhibitor loaded in Nanoparticles hydrogels. Thus, the effectiveness of NP-loaded hydrogel carrying FGFBP1 inhibitors will be generated, and validated by CNR Nanotec Lecce (Aim 1, UO 2), whose biochemical release will be tested by mass spectrometry by UO 3 ASL3 Lecce; their biological effectiveness will be validated on myelinated Schwann cells neuronal cocultures seeded with human organoids carrying NP-loaded hydrogels (Aim 2 - OSR), and in vivo in TPAC mice, a recently developed animal model of PDAC, whose pancreas will be injected with NP-loaded hydrogels (Aim 3 - OSR).

Study duration Duration of enrollment: 18 months Duration of total follow-up: no follow-up needed for enrolled patients Duration of total study period: 24 months

STUDY POPULATION Study Participants Adult patients undergoing surgical pancreatic resection, as per clinical practice, with clinically and radiologically confirmed diagnosis of ductal adenocarcinoma. All patients will be enrolled at the OSR Pancreatic and Transplant Surgery Unit.

Inclusion Criteria