
Establishment of patient derived xenografts as functional testing of lung cancer aggressiveness
Author(s) -
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
Publication year - 2017
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/s41598-017-06912-7
Subject(s) - lung cancer , medicine , oncology , cancer , stage (stratigraphy) , vimentin , bioinformatics , biology , immunohistochemistry , paleontology
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 max 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.