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A comprehensively characterized large panel of head and neck cancer patient-derived xenografts identifies the mTOR inhibitor everolimus as potential new treatment option

Item Type:Article
Title:A comprehensively characterized large panel of head and neck cancer patient-derived xenografts identifies the mTOR inhibitor everolimus as potential new treatment option
Creators Name:Klinghammer, K. and Raguse, J.D. and Plath, T. and Albers, A.E. and Joehrens, K. and Zakarneh, A. and Brzezicha, B. and Wulf-Goldenberg, A. and Keilholz, U. and Hoffmann, J. and Fichtner, I.
Abstract:Patient-derived xenograft (PDX) models have shown to reflect original patient tumors better than any other preclinical model. We embarked in a study establishing a large panel of head and neck squamous cell carcinomas PDX for biomarker analysis and evaluation of established and novel compounds. Out of 115 transplanted specimens 52 models were established of which 29 were characterized for response to docetaxel, cetuximab, methotrexate, carboplatin, 5-fluorouracil and everolimus. Further, tumors were subjected to sequencing analysis and gene expression profiling of selected mTOR pathway members. Most frequent response was observed for docetaxel and cetuximab. Responses to carboplatin, 5-fluorouracil and methotrexate were moderate. Everolimus revealed activity in the majority of PDX. Mutational profiling and gene expression analysis did not reveal a predictive biomarker for everolimus even though by trend RPS6KB1 mRNA expression was associated with response. In conclusion we demonstrate a comprehensively characterized panel of head and neck cancer PDX models, which represent a valuable and renewable tissue resource for evaluation of novel compounds and associated biomarkers.
Keywords:Xenograft, Head and Neck Cancer, PDX, Everolimus, PI3K, Patient Avatar, mTor, HNSCC, Animals, Mice
Source:International Journal of Cancer
ISSN:0020-7136
Publisher:Wiley-Blackwell (Switzerland)
Volume:136
Number:12
Page Range:2940-2948
Date:15 June 2015
Official Publication:https://doi.org/10.1002/ijc.29344
PubMed:View item in PubMed

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