PDX-derived organoids model in vivo drug response and secrete biomarkers

• DOI: 10.1172/jci.insight.135544
• Publication Date: 2020-09-29T17:54:04Z
• Authors: Ling Huang; Bruno Bockorny; Indranil Paul; Dipikaa Akshinthala; Pierre-Oliver Fra...; Omar Gandarilla; Arindam Bose; Veronica Sanchez-...; Emily E. Rouse; Sylvain D. Lehoux; Nicole Pandell; Christine M. Lim; John G. Clohessy; Joseph Grossman; Raul Gonzalez; Sofia Perea Del Pino; George Daaboul; Mandeep S. Sawhney; Steven D. Freedman; Alexander Kleger; Richard D. Cummings; Andrew Emili; Lakshmi B. Muthus...; Manuel Hidalgo; Senthil K. Muthus...
• Keywords: Organoid; Drug response

Patient-derived organoid models are proving to be a powerful platform for both basic and translational studies. Here we conduct methodical analysis of pancreatic ductal adenocarcinoma (PDAC) tumor drug response in paired patient-derived xenograft (PDX) PDX-derived (PXO) grown under WNT-free culture conditions. We report specific relationship between area the curve value dose vivo growth, irrespective treatment. In addition, analyzed glycome PDX PXO demonstrate that PXOs recapitulate glycan landscape. identify core set 57 N-glycans detected all 10 represent 50%–94% relative abundance each models. Last, developed secreted biomarker discovery pipeline using media supernatant cultures identified potentially new extracellular vesicle (EV) protein markers. validated our findings plasma samples from patients with PDAC, benign gastrointestinal diseases, chronic pancreatitis discovered 4 EV proteins potential circulating biomarkers PDAC. Thus, utility not only model responses but also serve as discovering clinically actionable serologic biomarkers.