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

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 uniqu...

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Bibliographic Details
Published in:	Scientific reports 2017-07, Vol.7 (1), p.6689-12, Article 6689
Main Authors:	Moro, Massimo, Bertolini, Giulia, Caserini, Roberto, Borzi, Cristina, Boeri, Mattia, Fabbri, Alessandra, Leone, Giorgia, Gasparini, Patrizia, Galeone, Carlotta, Pelosi, Giuseppe, Roz, Luca, Sozzi, Gabriella, Pastorino, Ugo
Format:	Article
Language:	eng
Subjects:	CXCR4 protein Grafting Lung cancer Non-small cell lung carcinoma Patients Stem cells Tumors Vimentin Xenografts
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Summary:	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 SUV 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.
ISSN:	2045-2322 2045-2322