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Article

Patient-Derived Explants of Colorectal Cancer: Histopathological and Molecular Analysis of Long-Term Cultures

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Serviço de Anatomia Patológica, Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG, EPE), Rua Prof. Lima Basto, 1099-023 Lisboa, Portugal
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NOVA Medical School, Universidade Nova de Lisboa, Campo dos Mártires da Pátria 130, 1169-056 Lisboa, Portugal
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Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2780-901 Oeiras, Portugal
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Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Av. da República, 2780-157 Oeiras, Portugal
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Unidade de Investigação em Patobiologia Molecular (UIPM), Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG, EPE), Rua Prof. Lima Basto, 1099-023 Lisboa, Portugal
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Faculdade de Medicina da Universidade de Lisboa, Avenida Prof. Egas Moniz MB, 1649-028 Lisboa, Portugal
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Abbvie Inc., 1 North Waukegan Road, North Chicago, IL 60064-6098, USA
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Serviço de Gastrenterologia, Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG, EPE), Rua Prof. Lima Basto, 1099-023 Lisboa, Portugal
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The Discoveries Centre for Regenerative and Precision Medicine, Lisbon Campus, Av. da República, 2780-157 Oeiras, Portugal
*
Authors to whom correspondence should be addressed.
Sara da Mata and Teresa Franchi-Mendes equally contributed to this work.
Academic Editor: Nyall London
Cancers 2021, 13(18), 4695; https://doi.org/10.3390/cancers13184695
Received: 31 August 2021 / Accepted: 14 September 2021 / Published: 19 September 2021
(This article belongs to the Special Issue Applications and Advances in Organoids for Cancer Research)
Colorectal cancer is the third most common cancer type among men and women. Prescription of medical treatments for cancer often relies on a process of trial and potential error, more recently guided by patient stratification based on biomarkers. Nonetheless, available biomarkers do not accurately predict patient response and there is a need for predictive and translational models to provide proper clinical information on treatment guidance. Herein, we developed an ex vivo model of colorectal cancer, using fresh tumour samples to establish explant cultures, taking advantage of agitation-based culture systems. We performed a thorough characterisation over one month in culture and observed preservation of original tumour genetic features and partial preservation of architecture and non-malignant cells that compose the tumour microenvironment. Our findings highlight the importance of detailed model characterisation and support the applicability of our model in pre- and co-clinical settings.
Colorectal cancer (CRC) is one of the most common cancers worldwide. Although short-term cultures of tumour sections and xenotransplants have been used to determine drug efficacy, the results frequently fail to confer clinically useful information. Biomarker discovery has changed the paradigm for advanced CRC, though the presence of a biomarker does not necessarily translate into therapeutic success. To improve clinical outcomes, translational models predictive of drug response are needed. We describe a simple method for the fast establishment of CRC patient-derived explant (CRC-PDE) cultures from different carcinogenesis pathways, employing agitation-based platforms. A total of 26 CRC-PDE were established and a subset was evaluated for viability (n = 23), morphology and genetic key alterations (n = 21). CRC-PDE retained partial tumor glandular architecture and microenvironment features were partially lost over 4 weeks of culture. Key proteins (p53 and Mismatch repair) and oncogenic driver mutations of the original tumours were sustained throughout the culture. Drug challenge (n = 5) revealed differential drug response from distinct CRC-PDE cases. These findings suggest an adequate representation of the original tumour and highlight the importance of detailed model characterisation. The preservation of key aspects of the CRC microenvironment and genetics supports CRC-PDE potential applicability in pre- and co-clinical settings, as long as temporal dynamics are considered. View Full-Text
Keywords: colorectal cancer; patient-derived explants; translational models colorectal cancer; patient-derived explants; translational models
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MDPI and ACS Style

da Mata, S.; Franchi-Mendes, T.; Abreu, S.; Filipe, B.; Morgado, S.; Mesquita, M.; Albuquerque, C.; Fonseca, R.; Santo, V.E.; Boghaert, E.R.; Rosa, I.; Brito, C. Patient-Derived Explants of Colorectal Cancer: Histopathological and Molecular Analysis of Long-Term Cultures. Cancers 2021, 13, 4695. https://doi.org/10.3390/cancers13184695

AMA Style

da Mata S, Franchi-Mendes T, Abreu S, Filipe B, Morgado S, Mesquita M, Albuquerque C, Fonseca R, Santo VE, Boghaert ER, Rosa I, Brito C. Patient-Derived Explants of Colorectal Cancer: Histopathological and Molecular Analysis of Long-Term Cultures. Cancers. 2021; 13(18):4695. https://doi.org/10.3390/cancers13184695

Chicago/Turabian Style

da Mata, Sara, Teresa Franchi-Mendes, Sofia Abreu, Bruno Filipe, Sónia Morgado, Marta Mesquita, Cristina Albuquerque, Ricardo Fonseca, Vítor E. Santo, Erwin R. Boghaert, Isadora Rosa, and Catarina Brito. 2021. "Patient-Derived Explants of Colorectal Cancer: Histopathological and Molecular Analysis of Long-Term Cultures" Cancers 13, no. 18: 4695. https://doi.org/10.3390/cancers13184695

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