Journal article
Clinical utility of patient-derived xenografts to determine biomarkers of prognosis and map resistance pathways in EGFR-mutant lung adenocarcinoma
EL Stewart, C Mascaux, NA Pham, S Sakashita, J Sykes, L Kim, N Yanagawa, G Allo, K Ishizawa, D Wang, CQ Zhu, M Li, C Ng, N Liu, M Pintilie, P Martin, T John, I Jurisica, NB Leighl, BG Neel Show all
Journal of Clinical Oncology | Published : 2015
Abstract
Purpose: Although epidermal growth factor receptor (EGFR) -mutated adenocarcinomas initially have high response rates to EGFR tyrosine kinase inhibitors (TKIs), most patients eventually develop resistance. Patient-derived xenografts (PDXs) are considered preferred preclinical models to study the biology of patient tumors. EGFR-mutant PDX models may be valuable tools to study the biology of these tumors and to elucidate mechanisms of resistance to EGFR-targeted therapies. Methods: Surgically resected early-stage non-small-cell lung carcinoma (NSCLC) tumors were implanted into nonobese diabetic severe combined immune deficient (NOD-SCID) mice. EGFR TKI treatment was initiated at tumor volumes ..
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Funding Acknowledgements
Supported by the Ontario Research Fund Research Excellence Award RE-03-020, Canadian Cancer Society (CCS) Research Institute Grants No. 020527 and No. 701595, and CCS and Rachelle Archambault Innovation Grant No. 701637; the Ontario Premier's Summit Award to F.A.S.; Princess Margaret Cancer Foundation; and the Ontario Ministry of Health and Long Term Care. E.L.S. was partially supported by the Terry Fox Foundation Strategic Training Initiative in Health Research Excellence in Radiation Research for the 21st Century at Canadian Institutes of Health Research (CIHR), Ontario Graduate Scholarship, and Graduate Ontario Student Opportunity Trust Fund. C.M. was supported by research grants from Boehringer-Ingelheim Canada and from the Televie (Fonds de la Recherche Scientifique-Fonds National de la Recherche Scientifique, Belgium). S.S, L.K., N.Y., and G.A. are supported by the Terry Fox Foundation Training Program in Molecular Pathology of Cancer at CIHR (STP 53912). G.L. holds the Alan B. Brown Chair in Molecular Genetics and Cancer Care Ontario Chair in Therapeutics, M.-S.T. holds the M. Qasim Choksi Chair in Lung Cancer Translational Research, and F.A.S. holds the Scott Taylor Chair in Lung Cancer Research. N.B.L. holds the OSI Pharmaceuticals Foundation Chair in Cancer New Drug Development. I.J. holds a Canada Research Chair in Integrative Cancer Informatics.