Evaluation of the influence of Cancer-Associated Fibroblasts on Patient-Derived Organoids in Pancreatic Cancer

Pancreatic Ductal Adenocarcinoma (PDAC) is the sixth-leading cause of cancer mortality worldwide and is characterized by the lowest survival rate after five years among all cancers. The lack of specific symptoms and effective screening methods typically results in a late-stage diagnosis, when the disease has often metastasized and is no longer eligible for surgical intervention. PDAC is characterized by a prominent stromal microenvironment, where the key components are the Cancer Associated Fibroblasts (CAF); studies show that they are able to promote tumor progression, metastasis, and therapy resistance. The aim of this study is to functionally evaluate two lines of PDAC patient-derived organoid (PDO): one that has undergone pre-treatment with FOLFIRINOX and one treatment-naïve line, in the presence or absence of conditioned medium from patient-matched CAFs. In particular, proliferation, invasion, and chemoresistance of PDO were investigated in order to elucidate in which way CAF-secreted factors are able to influence tumor behavior. Identifying the pathways in tumor cells that are modulated by CAFs and the mechanisms through which these interactions occur in different patients, can help to develop novel therapeutic strategies and advance personalized medicine for PDAC.