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Acquired Resistance to Crizotinib in NSCLC with MET Exon 14 Skipping

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Presentation on theme: "Acquired Resistance to Crizotinib in NSCLC with MET Exon 14 Skipping"— Presentation transcript:

1 Acquired Resistance to Crizotinib in NSCLC with MET Exon 14 Skipping
Rebecca S. Heist, MD, MPH, Lecia V. Sequist, MD, MPH, Darrell Borger, PhD, Justin F. Gainor, MD, Ronald S. Arellano, MD, Long P. Le, MD, PhD, Dora Dias-Santagata, PhD, Jeffrey W. Clark, MD, Jeffrey A. Engelman, MD, PhD, Alice T. Shaw, MD, PhD, A. John Iafrate, MD, PhD  Journal of Thoracic Oncology  Volume 11, Issue 8, Pages (August 2016) DOI: /j.jtho Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

2 Figure 1 Computed tomography (CT) scans of a patient with MET proto-oncogene, receptor tyrosine kinase gene (MET) exon 14 skipping showing response and subsequent progression while the patient was receiving crizotinib. (A) Contrast-enhanced coronal CT scan before crizotinib. White arrows indicate hepatic metastases. (B) Contrast-enhanced coronal CT scan at best response to crizotinib. White arrows indicate interval decrease in size of hepatic metastases. (C) Contrast-enhanced coronal CT scan at time of progressive disease. White arrow indicates a new liver metastasis on which a biopsy was performed. Journal of Thoracic Oncology  , DOI: ( /j.jtho ) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

3 Figure 2 Emergence of a secondary MET proto-oncogene, receptor tyrosine kinase gene (MET) D1228N mutation and proto-oncogene, receptor tyrosine kinase (MET) protein activation upon development of acquired resistance to crizotinib in the setting of MET exon 14 skipping. (A) Sequence alignment shows the original MET exon 14 skipping D1010H mutation and the emergence of the secondary MET D1228N mutation. Immunohistochemical testing identified high levels of total MET protein (B), as well as high levels of active MET protein through immunohistochemical testing for phospho-MET Y1349 (C). Journal of Thoracic Oncology  , DOI: ( /j.jtho ) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

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