Development of patient-derived orthotopic xenografts from metastatic colorectal cancer in nude mice

Liver metastasis is the major cause of death for patients with colorectal cancer. Despite treatment with surgery and chemotherapy, patient outcomes are quite unfavourable. Thus, there is an urgent need to develop new treatment strategies with the associated establishment of good animal models. Metas...

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Bibliographic Details
Published in:	Journal of drug targeting Vol. 27; no. 9; pp. 943 - 949
Main Authors:	Roque-Lima, Bruno, Roque, Caroline Correa de Tulio Augusto, Begnami, Maria Dirlei, Peresi, Patricia, Lima, Eduardo Nobrega Pereira, Mello, Celso Abdon Lopes de, Coimbra, Felipe JoséFernandez, Chojniak, Rubens, Goss Santos, Tiago
Format:	Journal Article
Language:	English
Published:	England Taylor & Francis 21-10-2019
Subjects:	colorectal cancer metastasis Orthotopic xenograft preclinical model Orthotopic xenograft colorectal cancer preclinical model metastasis
Online Access:	Get full text
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Summary:	Liver metastasis is the major cause of death for patients with colorectal cancer. Despite treatment with surgery and chemotherapy, patient outcomes are quite unfavourable. Thus, there is an urgent need to develop new treatment strategies with the associated establishment of good animal models. Metastatic disease can be modelled using patient-derived orthotopic xenografts, which accurately replicate intra-tumoral heterogeneity so that various chemotherapeutic agents can be tested on individual tumours to aid in clinical decision-making. The objective of this study was to develop metastatic colorectal tumours in athymic nude mice by implanting fresh tumour fragments into mouse liver parenchyma. Metastatic tumours were successfully propagated in mice following transplantation from human patients, then serially implanted in second and third-generation mice. Morphologic and immunohistochemical characteristics indicate that xenografts recreate the tumour architecture and mismatch repair gene expression for MLH1, MSH2, MSH1, and PMS2. After tumour implantation during the first passage, the time of tumour growth decreased without loss of tumour identity. Post-transplantation lymphoproliferative disease was observed in one case. This pilot study was successful in establishing the institutional PDX preclinical platform to study new therapeutic strategies, disease progression biomarkers, and treatment responsiveness.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1061-186X 1029-2330
DOI:	10.1080/1061186X.2018.1509983