Validation of a Novel EUS-FNB-Derived Organoid Co-Culture System for Drug Screening in Patients with Pancreatic Cancer

Simple Summary Pancreatic cancer is a devastating disease with a 5-year survival rate of 12%. Only about 20% of patients are candidates for curative surgery, while the majority receive palliative chemotherapy or best supportive care. Recently, testing chemotherapeutical agents on patient-derived 3-dimensional cultures (organoids) of cancer cells has provided hope that personalized treatment may soon become a reality. However, most of these models only include tumor cells and not cells of the supporting tissue, which have been shown to play a critical role in cancer progression. In this study, we created a co-culture including both tumor and stromal cells from endoscopic ultrasound-guided biopsies and showed that an interaction occurs between the cell types in our model. It may therefore be a step towards better prediction of therapeutic response in the future. We also discuss the limitations of creating these types of models by using endoscopic biopsies from primary tumors. Cancer-associated fibroblasts (CAFs) have been shown to impact the chemosensitivity of patient-derived tumor organoids (PDTOs). However, the published literature comparing PDTO response to clinical outcome does not include CAFs in the models. Here, a co-culture model was created using PDTOs and CAFs derived from endoscopic ultrasound-guided fine-needle biopsies (EUS-FNBs) for potential use in drug screening applications. Co-cultures were established, and growth was compared to monocultures using image metrics and a commercially available assay. We were able to establish and expand validated malignant PDTOs from 19.2% of adenocarcinomas from EUS-FNBs. CAFs could be established from 25% of the samples. The viability of PDTOs in the mixed cell co-culture could be isolated using image metrics. The addition of CAFs promoted PDTO growth in half of the established co-cultures. These results show that co-cultures can be established from tiny amounts of tissue provided by EUS-FNB. An increased growth of PDTOs was shown in co-cultures, suggesting that the present setup successfully models CAF-PDTO interaction. Furthermore, we demonstrated that standard validation techniques may be insufficient to detect contamination with normal cells in PDTO cultures established from primary tumor core biopsies.