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Patient-derived explants (PDEs) as a powerful preclinical platform for anti-cancer drug and biomarker discovery
Preclinical models that can accurately predict outcomes in the clinic are much sought after in the field of cancer drug discovery and development. Existing models such as organoids and patient-derived xenografts have many advantages, but they suffer from the drawback of not contextually preserving h...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078311/ https://www.ncbi.nlm.nih.gov/pubmed/31894140 http://dx.doi.org/10.1038/s41416-019-0672-6 |
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author | Powley, Ian R. Patel, Meeta Miles, Gareth Pringle, Howard Howells, Lynne Thomas, Anne Kettleborough, Catherine Bryans, Justin Hammonds, Tim MacFarlane, Marion Pritchard, Catrin |
author_facet | Powley, Ian R. Patel, Meeta Miles, Gareth Pringle, Howard Howells, Lynne Thomas, Anne Kettleborough, Catherine Bryans, Justin Hammonds, Tim MacFarlane, Marion Pritchard, Catrin |
author_sort | Powley, Ian R. |
collection | PubMed |
description | Preclinical models that can accurately predict outcomes in the clinic are much sought after in the field of cancer drug discovery and development. Existing models such as organoids and patient-derived xenografts have many advantages, but they suffer from the drawback of not contextually preserving human tumour architecture. This is a particular problem for the preclinical testing of immunotherapies, as these agents require an intact tumour human-specific microenvironment for them to be effective. In this review, we explore the potential of patient-derived explants (PDEs) for fulfilling this need. PDEs involve the ex vivo culture of fragments of freshly resected human tumours that retain the histological features of original tumours. PDE methodology for anti-cancer drug testing has been in existence for many years, but the platform has not been widely adopted in translational research facilities, despite strong evidence for its clinical predictivity. By modifying PDE endpoint analysis to include the spatial profiling of key biomarkers by using multispectral imaging, we argue that PDEs offer many advantages, including the ability to correlate drug responses with tumour pathology, tumour heterogeneity and changes in the tumour microenvironment. As such, PDEs are a powerful model of choice for cancer drug and biomarker discovery programmes. |
format | Online Article Text |
id | pubmed-7078311 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-70783112020-03-18 Patient-derived explants (PDEs) as a powerful preclinical platform for anti-cancer drug and biomarker discovery Powley, Ian R. Patel, Meeta Miles, Gareth Pringle, Howard Howells, Lynne Thomas, Anne Kettleborough, Catherine Bryans, Justin Hammonds, Tim MacFarlane, Marion Pritchard, Catrin Br J Cancer Review Article Preclinical models that can accurately predict outcomes in the clinic are much sought after in the field of cancer drug discovery and development. Existing models such as organoids and patient-derived xenografts have many advantages, but they suffer from the drawback of not contextually preserving human tumour architecture. This is a particular problem for the preclinical testing of immunotherapies, as these agents require an intact tumour human-specific microenvironment for them to be effective. In this review, we explore the potential of patient-derived explants (PDEs) for fulfilling this need. PDEs involve the ex vivo culture of fragments of freshly resected human tumours that retain the histological features of original tumours. PDE methodology for anti-cancer drug testing has been in existence for many years, but the platform has not been widely adopted in translational research facilities, despite strong evidence for its clinical predictivity. By modifying PDE endpoint analysis to include the spatial profiling of key biomarkers by using multispectral imaging, we argue that PDEs offer many advantages, including the ability to correlate drug responses with tumour pathology, tumour heterogeneity and changes in the tumour microenvironment. As such, PDEs are a powerful model of choice for cancer drug and biomarker discovery programmes. Nature Publishing Group UK 2020-01-02 2020-03-17 /pmc/articles/PMC7078311/ /pubmed/31894140 http://dx.doi.org/10.1038/s41416-019-0672-6 Text en © The Author(s) 2020 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Review Article Powley, Ian R. Patel, Meeta Miles, Gareth Pringle, Howard Howells, Lynne Thomas, Anne Kettleborough, Catherine Bryans, Justin Hammonds, Tim MacFarlane, Marion Pritchard, Catrin Patient-derived explants (PDEs) as a powerful preclinical platform for anti-cancer drug and biomarker discovery |
title | Patient-derived explants (PDEs) as a powerful preclinical platform for anti-cancer drug and biomarker discovery |
title_full | Patient-derived explants (PDEs) as a powerful preclinical platform for anti-cancer drug and biomarker discovery |
title_fullStr | Patient-derived explants (PDEs) as a powerful preclinical platform for anti-cancer drug and biomarker discovery |
title_full_unstemmed | Patient-derived explants (PDEs) as a powerful preclinical platform for anti-cancer drug and biomarker discovery |
title_short | Patient-derived explants (PDEs) as a powerful preclinical platform for anti-cancer drug and biomarker discovery |
title_sort | patient-derived explants (pdes) as a powerful preclinical platform for anti-cancer drug and biomarker discovery |
topic | Review Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078311/ https://www.ncbi.nlm.nih.gov/pubmed/31894140 http://dx.doi.org/10.1038/s41416-019-0672-6 |
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