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

Massimo Moro, Bertolini Giulia, Caserini Roberto, Borzi Cristina, Boeri Mattia, Fabbri Alessandra, Leone Giorgia, Gasparini Patrizia, Galeone Carlotta, Pelosi Giuseppe, Roz Luca, Sozzi Gabriella, Pastorino Ugo

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number6689
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - Dec 1 2017

ASJC Scopus subject areas

  • General

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