Abstract 163: Establishment of pancreatic ductal adenocarcinoma organoids model using endoscopic ultrasonography-guided fine needle biopsy: a new window into understanding pancreatic ductal adenocarcinoma tumor biology

Abstract

Abstract Background & Aims: Tumor biology studies of pancreatic ductal adenocarcinoma (PDAC) used surgical specimens, even though most PDACs are unresectable. The aims of the study were to 1) establish PDAC organoids platform from endoscopic ultrasonography (EUS)-guided fine needle biopsy (FNB), 2) investigate clinicopathologic and genomic characterization, and 3) find out the clinical applicability of the patient-derived PDAC organoids model from PDAC diagnosis to treatment timeline. Methods: The patients with suspected PDACs were enrolled prospectively, and PDAC minimal specimens were acquired from EUS-guided FNB at Samsung Medical Center from 2015 to 2019. Results: Ninety-four PDAC organoids were successfully established (94/113, 83.2%) via EUS-guided FNB within 8.2±2.6 days. Clinical factors were also analyzed associated with the success rate in establishing PDAC organoids; specimens with high cellularity (>10 clusters) were an independent factor in multivariate analysis. Whole exome sequencing showed the high concordance between primary PDAC and its organoid and more enriched genetic alterations in organoids. In addition, the high-throughput screening (HTS) drug test revealed that the clinical correlation with real-world data was 12 out of 15 between PDAC organoids and the chemotherapeutic response of the study patients. Whole-transcriptome sequencing identified genes and pathways associated with the drug responses. Conclusions: We have achieved the PDAC organoid platform in a high success rate via EUS-guided FNB, and the concordance between primary PDAC and its organoid seems very high. More importantly, the HTS drug test showed that PDAC organoids may well reflect clinical chemotherapeutic response and may also be used as the “Patient Avatar Model” in clinical practice on time. Citation Format: Hyemin Kim, Hongui Cha, Se-Hoon Lee, Joo Kyung Park. Establishment of pancreatic ductal adenocarcinoma organoids model using endoscopic ultrasonography-guided fine needle biopsy: a new window into understanding pancreatic ductal adenocarcinoma tumor biology [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 163.