Establishment of patient derived xenografts as functional testing of lung cancer aggressiveness.
Sci Rep. 2017 07 27;7(1):6689
Authors: Moro M, Bertolini G, Caserini R, Borzi C, Boeri M, Fabbri A, Leone G, Gasparini P, Galeone C, Pelosi G, Roz L, Sozzi G, Pastorino U
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.
PMID: 28751748 [PubMed – indexed for MEDLINE]