PDX-derived organoids model in vivo drug response and secrete biomarkers
| العنوان: | PDX-derived organoids model in vivo drug response and secrete biomarkers |
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| المؤلفون: | Senthil K. Muthuswamy, Steven D. Freedman, Andrew Emili, George G. Daaboul, Omar Gandarilla, Sofia Perea Del Pino, Sylvain Lehoux, Veronica Sanchez-Gonzalez, Emily E Rouse, Lakshmi Muthuswamy, Joseph Grossman, Dipikaa Akshinthala, John G. Clohessy, Ling Huang, Arindam Bose, Nicole Pandell, Christine Maria Lim, Manuel Hidalgo, Alexander Kleger, Bruno Bockorny, Richard D. Cummings, Raul S. Gonzalez, Pierre-Oliver Frappart, Mandeep S. Sawhney, Indranil Paul |
| المصدر: | JCI Insight, Vol 5, Iss 21 (2020) JCI Insight |
| بيانات النشر: | American Society for Clinical Investigation, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Glycobiology, Mice, Nude, Antineoplastic Agents, Apoptosis, Biology, Extracellular Vesicles, Mice, 03 medical and health sciences, 0302 clinical medicine, Polysaccharides, In vivo, Biomarkers, Tumor, Tumor Cells, Cultured, Organoid, medicine, Animals, Humans, Secretion, Biomarker discovery, Cancer, Cell Proliferation, General Medicine, Extracellular vesicle, Prognosis, medicine.disease, Xenograft Model Antitumor Assays, Glycome, Gene Expression Regulation, Neoplastic, Organoids, Pancreatic Neoplasms, Disease Models, Animal, 030104 developmental biology, Technical Advance, Oncology, 030220 oncology & carcinogenesis, Cancer research, Medicine, Carcinoma, Pancreatic Ductal |
| الوصف: | Patient-derived organoid models are proving to be a powerful platform for both basic and translational studies. Here we conduct a methodical analysis of pancreatic ductal adenocarcinoma (PDAC) tumor organoid drug response in paired patient-derived xenograft (PDX) and PDX-derived organoid (PXO) models grown under WNT-free culture conditions. We report a specific relationship between area under the curve value of organoid drug dose response and in vivo tumor growth, irrespective of the drug treatment. In addition, we analyzed the glycome of PDX and PXO models and demonstrate that PXOs recapitulate the in vivo glycan landscape. In addition, we identify a core set of 57 N-glycans detected in all 10 models that represent 50%–94% of the relative abundance of all N-glycans detected in each of the models. Last, we developed a secreted biomarker discovery pipeline using media supernatant of organoid cultures and identified potentially new extracellular vesicle (EV) protein markers. We validated our findings using plasma samples from patients with PDAC, benign gastrointestinal diseases, and chronic pancreatitis and discovered that 4 EV proteins are potential circulating biomarkers for PDAC. Thus, we demonstrate the utility of organoid cultures to not only model in vivo drug responses but also serve as a powerful platform for discovering clinically actionable serologic biomarkers. Pancreatic ductal adenocarcinoma tumor organoids are effective models for predicting in vivo drug response and discovering new biomarkers. |
| تدمد: | 2379-3708 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e00487f403ddf096485243ae6bd50244Test https://doi.org/10.1172/jci.insight.135544Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....e00487f403ddf096485243ae6bd50244 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23793708 |
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