Patient-Derived Organoid Models of Human Neuroendocrine Carcinoma

Gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC) is a poorly understood disease with limited treatment options. A better understanding of this disease would greatly benefit from the availability of representative preclinical models. Here, we present the potential of tumor organoids, three-d...

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Vydáno v:Frontiers in endocrinology (Lausanne) Ročník 12; s. 627819
Hlavní autoři: Dijkstra, Krijn K., van den Berg, José G., Weeber, Fleur, van de Haar, Joris, Velds, Arno, Kaing, Sovann, Peters, Dennis D. G. C., Eskens, Ferry A. L. M., de Groot, Derk-Jan A., Tesselaar, Margot E. T., Voest, Emile E.
Médium: Journal Article
Jazyk:angličtina
Vydáno: Switzerland Frontiers Media S.A 11.03.2021
Témata:
Cell Death - drug effects
Cell Line, Tumor
Cisplatin - pharmacology
Cisplatin - therapeutic use
disease modeling
DNA Mismatch Repair - drug effects
Endocrinology
Everolimus - pharmacology
Everolimus - therapeutic use
extrapulmonary neuroendocrine carcinoma
gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC)
Gene Dosage
Humans
Intestinal Neoplasms - drug therapy
Intestinal Neoplasms - genetics
Intestinal Neoplasms - pathology
Ki-67 Antigen - metabolism
Models, Biological
Mutation - genetics
Neuroendocrine Tumors - drug therapy
Neuroendocrine Tumors - genetics
Neuroendocrine Tumors - pathology
organoids
Organoids - drug effects
Organoids - metabolism
Organoids - pathology
Pancreatic Neoplasms - drug therapy
Pancreatic Neoplasms - genetics
Pancreatic Neoplasms - pathology
pre-clinical models
Stomach Neoplasms - drug therapy
Stomach Neoplasms - genetics
Stomach Neoplasms - pathology
Whole Exome Sequencing
organoids
pre-clinical models
disease modeling
gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC)
extrapulmonary neuroendocrine carcinoma
ISSN:1664-2392, 1664-2392
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Shrnutí:Gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC) is a poorly understood disease with limited treatment options. A better understanding of this disease would greatly benefit from the availability of representative preclinical models. Here, we present the potential of tumor organoids, three-dimensional cultures of tumor cells, to model GEP-NEC. We established three GEP-NEC organoid lines, originating from the stomach and colon, and characterized them using DNA sequencing and immunohistochemistry. Organoids largely resembled the original tumor in expression of synaptophysin, chromogranin and Ki-67. Models derived from tumors containing both neuroendocrine and non-neuroendocrine components were at risk of overgrowth by non-neuroendocrine tumor cells. Organoids were derived from patients treated with cisplatin and everolimus and for the three patients studied, organoid chemosensitivity paralleled clinical response. We demonstrate the feasibility of establishing NEC organoid lines and their potential applications. Organoid culture has the potential to greatly extend the repertoire of preclinical models for GEP-NEC, supporting drug development for this difficult-to-treat tumor type.
Bibliografie:ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-1
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Present address: Krijn K. Dijkstra, Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, United Kingdom
Edited by: Priya Dedhia, The Ohio State University, United States
This article was submitted to Cancer Endocrinology, a section of the journal Frontiers in Endocrinology
Reviewed by: Ilaria Marinoni, University of Bern, Switzerland; Ronald De Krijger, Princess Maxima Center for Pediatric Oncology, Netherlands
ISSN:1664-2392
1664-2392
DOI:10.3389/fendo.2021.627819