Dantes, Z.* ; Yen, H.Y.* ; Pfarr, N.* ; Winter, C.* ; Steiger, K.* ; Muckenhuber, A.* ; Hennig, A.* ; Lange, S.* ; Engleitner, T.* ; Öllinger, R.* ; Maresch, R.* ; Orben, F.* ; Heid, I.* ; Kaissis, G.* ; Shi, K.* ; Topping, G.* ; Stögbauer, F.* ; Wirth, M.* ; Peschke, K.* ; Papargyriou, A.* ; Rezaee-Oghazi, M.* ; Feldmann, K.* ; Schäfer, A.P.* ; Ranjan, R.* ; Lubeseder-Martellato, C.* ; Stange, D.E.* ; Welsch, T.* ; Martignoni, M.* ; Ceyhan, G.O.* ; Friess, H.* ; Herner, A.* ; Liotta, L.A.* ; Treiber, M.* ; von Figura, G.* ; Abdelhafez, M.* ; Klare, P.* ; Schlag, C.* ; Algül, H.* ; Siveke, J.* ; Braren, R.* ; Weirich, G.* ; Weichert, W.* ; Saur, D.* ; Rad, R.* ; Schmid, R.M.* ; Schneider, G.* ; Reichert, M.*
Implementing cell-free DNA of pancreatic cancer patient-derived organoids for personalized oncology.
JCI insight 5:e137809 (2020)
One of the major challenges in using pancreatic cancer patient-derived organoids (PDOs) in precision oncology is the time from biopsy to functional characterization. This is particularly true for endoscopic ultrasound-guided fine-needle aspiration biopsies, typically resulting in specimens with limited tumor cell yield. Here, we tested conditioned media of individual PDOs for cell-free DNA to detect driver mutations already early on during the expansion process to accelerate the genetic characterization of PDOs as well as subsequent functional testing. Importantly, genetic alterations detected in the PDO supernatant, collected as early as 72 hours after biopsy, recapitulate the mutational profile of the primary tumor, indicating suitability of this approach to subject PDOs to drug testing in a reduced time frame. In addition, we demonstrated that this workflow was practicable, even in patients for whom the amount of tumor material was not sufficient for molecular characterization by established means. Together, our findings demonstrate that generating PDOs from very limited biopsy material permits molecular profiling and drug testing. With our approach, this can be achieved in a rapid and feasible fashion with broad implications in clinical practice.
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Publication type
Article: Journal article
Document type
Scientific Article
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Keywords
Gastroenterology ; Oncology ; Translation
Keywords plus
Language
english
Publication Year
2020
Prepublished in Year
HGF-reported in Year
2020
ISSN (print) / ISBN
2379-3708
e-ISSN
2379-3708
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Volume: 5,
Issue: 15,
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Article Number: e137809
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Publisher
Clarivate
Publishing Place
Ann Arbor, Michigan
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0000-00-00
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0000-00-00
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0000-00-00
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Reviewing status
Peer reviewed
POF-Topic(s)
30205 - Bioengineering and Digital Health
Research field(s)
Enabling and Novel Technologies
PSP Element(s)
G-530014-001
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Copyright
Erfassungsdatum
2022-09-13