Establishment of patient derived xenografts as functional testing of lung cancer aggressiveness

Abstract Despite many years of research efforts, lung cancer still remains the leading cause of cancer deaths worldwide. Objective of this study was to set up a platform of non-small cell lung cancer patient derived xenografts (PDXs) faithfully representing primary tumour characteristics and offerin...

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Autores principales:	Massimo Moro, Giulia Bertolini, Roberto Caserini, Cristina Borzi, Mattia Boeri, Alessandra Fabbri, Giorgia Leone, Patrizia Gasparini, Carlotta Galeone, Giuseppe Pelosi, Luca Roz, Gabriella Sozzi, Ugo Pastorino
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a5c3a54063d1498f9a6a7e52bb320e62
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spelling	oai:doaj.org-article:a5c3a54063d1498f9a6a7e52bb320e622021-12-02T11:40:31ZEstablishment of patient derived xenografts as functional testing of lung cancer aggressiveness10.1038/s41598-017-06912-72045-2322https://doaj.org/article/a5c3a54063d1498f9a6a7e52bb320e622017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06912-7https://doaj.org/toc/2045-2322Abstract Despite many years of research efforts, lung cancer still remains the leading cause of cancer deaths worldwide. Objective of this study was to set up a platform of non-small cell lung cancer patient derived xenografts (PDXs) faithfully representing primary tumour characteristics and offering a unique tool for studying effectiveness of therapies at a preclinical level. We established 38 PDXs with a successful take rate of 39.2%. All models closely mirrored parental tumour characteristics although a selective pressure for solid patterns, vimentin expression and EMT was observed in several models. An increased grafting rate for tumours derived from patients with worse outcome (p = 0.006), higher stage (p = 0.038) and higher CD133+/CXCR4+/EpCAM− stem cell content (p = 0.019) was observed whereas a trend towards an association with SUVmax higher than 8 (p = 0.084) was detected. Kaplan Meier analyses showed a significantly worse (p = 0.0008) overall survival at 5 years in patients with grafted vs not grafted PDXs also after adjusting for tumour stage. Moreover, for 63.2% models, grafting was reached before clinical recurrence occurred. Our findings strengthen the relevance of PDXs as useful preclinical models closely reflecting parental patients tumours and highlight PDXs establishment as a functional testing of lung cancer aggressiveness and personalized therapies.Massimo MoroGiulia BertoliniRoberto CaseriniCristina BorziMattia BoeriAlessandra FabbriGiorgia LeonePatrizia GaspariniCarlotta GaleoneGiuseppe PelosiLuca RozGabriella SozziUgo PastorinoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Massimo Moro Giulia Bertolini Roberto Caserini Cristina Borzi Mattia Boeri Alessandra Fabbri Giorgia Leone Patrizia Gasparini Carlotta Galeone Giuseppe Pelosi Luca Roz Gabriella Sozzi Ugo Pastorino Establishment of patient derived xenografts as functional testing of lung cancer aggressiveness
description	Abstract Despite many years of research efforts, lung cancer still remains the leading cause of cancer deaths worldwide. Objective of this study was to set up a platform of non-small cell lung cancer patient derived xenografts (PDXs) faithfully representing primary tumour characteristics and offering a unique tool for studying effectiveness of therapies at a preclinical level. We established 38 PDXs with a successful take rate of 39.2%. All models closely mirrored parental tumour characteristics although a selective pressure for solid patterns, vimentin expression and EMT was observed in several models. An increased grafting rate for tumours derived from patients with worse outcome (p = 0.006), higher stage (p = 0.038) and higher CD133+/CXCR4+/EpCAM− stem cell content (p = 0.019) was observed whereas a trend towards an association with SUVmax higher than 8 (p = 0.084) was detected. Kaplan Meier analyses showed a significantly worse (p = 0.0008) overall survival at 5 years in patients with grafted vs not grafted PDXs also after adjusting for tumour stage. Moreover, for 63.2% models, grafting was reached before clinical recurrence occurred. Our findings strengthen the relevance of PDXs as useful preclinical models closely reflecting parental patients tumours and highlight PDXs establishment as a functional testing of lung cancer aggressiveness and personalized therapies.
format	article
author	Massimo Moro Giulia Bertolini Roberto Caserini Cristina Borzi Mattia Boeri Alessandra Fabbri Giorgia Leone Patrizia Gasparini Carlotta Galeone Giuseppe Pelosi Luca Roz Gabriella Sozzi Ugo Pastorino
author_facet	Massimo Moro Giulia Bertolini Roberto Caserini Cristina Borzi Mattia Boeri Alessandra Fabbri Giorgia Leone Patrizia Gasparini Carlotta Galeone Giuseppe Pelosi Luca Roz Gabriella Sozzi Ugo Pastorino
author_sort	Massimo Moro
title	Establishment of patient derived xenografts as functional testing of lung cancer aggressiveness
title_short	Establishment of patient derived xenografts as functional testing of lung cancer aggressiveness
title_full	Establishment of patient derived xenografts as functional testing of lung cancer aggressiveness
title_fullStr	Establishment of patient derived xenografts as functional testing of lung cancer aggressiveness
title_full_unstemmed	Establishment of patient derived xenografts as functional testing of lung cancer aggressiveness
title_sort	establishment of patient derived xenografts as functional testing of lung cancer aggressiveness
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/a5c3a54063d1498f9a6a7e52bb320e62
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Establishment of patient derived xenografts as functional testing of lung cancer aggressiveness

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