Publication
Title
Single-organoid analysis reveals clinically relevant treatment-resistant and invasive subclones in pancreatic cancer
Author
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal diseases, characterized by a treatment-resistant and invasive nature. In line with these inherent aggressive characteristics, only a subset of patients shows a clinical response to the standard of care therapies, thereby highlighting the need for a more personalized treatment approach. In this study, we comprehensively unraveled the intra-patient response heterogeneity and intrinsic aggressive nature of PDAC on bulk and single-organoid resolution. We leveraged a fully characterized PDAC organoid panel ( N  = 8) and matched our artificial intelligence-driven, live-cell organoid image analysis with retrospective clinical patient response. In line with the clinical outcomes, we identified patient-specific sensitivities to the standard of care therapies (gemcitabine-paclitaxel and FOLFIRINOX) using a growth rate-based and normalized drug response metric. Moreover, the single-organoid analysis was able to detect resistant as well as invasive PDAC organoid clones, which was orchestrates on a patient, therapy, drug, concentration and time-specific level. Furthermore, our in vitro organoid analysis indicated a correlation with the matched patient progression-free survival (PFS) compared to the current, conventional drug response readouts. This work not only provides valuable insights on the response complexity in PDAC, but it also highlights the potential applications (extendable to other tumor types) and clinical translatability of our approach in drug discovery and the emerging era of personalized medicine.
Language
English
Source (journal)
npj Precision Oncology / The Hormel Institute,University of Minnesota
Publication
Nature Publishing Group , 2023
ISSN
2397-768X
DOI
10.1038/S41698-023-00480-Y
Volume/pages
7 :1 (2023) , p. 1-14
Article Reference
128
ISI
001118015800001
Pubmed ID
38066116
Full text (Publisher's DOI)
Full text (open access)
UAntwerpen
Faculty/Department
Research group
Project info
Rationally designed drug combination screen in more physiologically relevant in vitro organoid models: can we improve personalized therapy for pancreatic cancer?
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identifier
Creation 10.12.2023
Last edited 16.02.2024
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