TY - JOUR
T1 - Patient-derived organoid models help define personalized management of gastrointestinal cancer
AU - Aberle, M. R.
AU - Burkhart, R. A.
AU - Tiriac, H.
AU - Olde Damink, S. W.M.
AU - Dejong, C. H.C.
AU - Tuveson, D. A.
AU - van Dam, R. M.
N1 - Funding Information:
The authors thank H. Clevers for sharing the organoid technology; all members of the laboratories of S.O.D., D.A.T. and R.A.B. for helpful discussions and suggestions throughout the course of this study; and the Cold Spring Harbor Cancer Center Support Grant (P30CA045508-29) for shared resources. This project was funded by the European Union subsidy programme Interreg as part of the OncoCare project Euregio Maas Rijn. This project was also funded by the Lustgarten Foundation, where D.A.T. is a distinguished scholar and Director of the Lust-garten Foundation-designated Laboratory of Pancreatic Cancer Research. D.A.T. is also supported by the Cold Spring Harbor Laboratory Association, the National Institutes of Health (5P30CA45508-29, 5P50CA101955-07, 1U10CA180944-04, 5U01CA168409-5, 1R01CA188134-01, 1R01CA190092-04) and the V Foundation. The authors also are grateful for support from the following: Stand Up to Cancer (AACRPS09 to D.A.T.) and Integrated Translational Science Center between SWOG and Cold Spring Harbor Laboratory (5U10CA180944-04 to D.A.T. and H.T.). Disclosure: The authors declare no conflict of interest.
Publisher Copyright:
© 2018 BJS Society Ltd Published by John Wiley & Sons Ltd
PY - 2018/1
Y1 - 2018/1
N2 - Background: The prognosis of patients with different gastrointestinal cancers varies widely. Despite advances in treatment strategies, such as extensive resections and the addition of new drugs to chemotherapy regimens, conventional treatment strategies have failed to improve survival for many tumours. Although promising, the clinical application of molecularly guided personalized treatment has proven to be challenging. This narrative review focuses on the personalization of cancer therapy using patient-derived three-dimensional ‘organoid’ models. Methods: A PubMed search was conducted to identify relevant articles. An overview of the literature and published protocols is presented, and the implications of these models for patients with cancer, surgeons and oncologists are explained. Results: Organoid culture methods have been established for healthy and diseased tissues from oesophagus, stomach, intestine, pancreas, bile duct and liver. Because organoids can be generated with high efficiency and speed from fine-needle aspirations, biopsies or resection specimens, they can serve as a personal cancer model. Personalized treatment could become a more standard practice by using these cell cultures for extensive molecular diagnosis and drug screening. Drug sensitivity assays can give a clinically actionable sensitivity profile of a patient's tumour. However, the predictive capability of organoid drug screening has not been evaluated in prospective clinical trials. Conclusion: High-throughput drug screening on organoids, combined with next-generation sequencing, proteomic analysis and other state-of-the-art molecular diagnostic methods, can shape cancer treatment to become more effective with fewer side-effects.
AB - Background: The prognosis of patients with different gastrointestinal cancers varies widely. Despite advances in treatment strategies, such as extensive resections and the addition of new drugs to chemotherapy regimens, conventional treatment strategies have failed to improve survival for many tumours. Although promising, the clinical application of molecularly guided personalized treatment has proven to be challenging. This narrative review focuses on the personalization of cancer therapy using patient-derived three-dimensional ‘organoid’ models. Methods: A PubMed search was conducted to identify relevant articles. An overview of the literature and published protocols is presented, and the implications of these models for patients with cancer, surgeons and oncologists are explained. Results: Organoid culture methods have been established for healthy and diseased tissues from oesophagus, stomach, intestine, pancreas, bile duct and liver. Because organoids can be generated with high efficiency and speed from fine-needle aspirations, biopsies or resection specimens, they can serve as a personal cancer model. Personalized treatment could become a more standard practice by using these cell cultures for extensive molecular diagnosis and drug screening. Drug sensitivity assays can give a clinically actionable sensitivity profile of a patient's tumour. However, the predictive capability of organoid drug screening has not been evaluated in prospective clinical trials. Conclusion: High-throughput drug screening on organoids, combined with next-generation sequencing, proteomic analysis and other state-of-the-art molecular diagnostic methods, can shape cancer treatment to become more effective with fewer side-effects.
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U2 - 10.1002/bjs.10726
DO - 10.1002/bjs.10726
M3 - Review article
C2 - 29341164
AN - SCOPUS:85040725673
VL - 105
SP - e48-e60
JO - Netherlands Journal of Surgery
JF - Netherlands Journal of Surgery
SN - 0007-1323
IS - 2
ER -