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Head Neck. 2011 Dec;33(12):1804-8. doi: 10.1002/hed.21478. Epub 2010 Jul 22.

Insulin-like growth factor-1 receptor inhibitor, AMG-479, in cetuximab-refractory head and neck squamous cell carcinoma.

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  • 1Division of Hematology/Oncology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.



Recurrent head and neck squamous cell carcinoma (HNSCC) remains a difficult cancer to treat. Here, we describe a patient with HNSCC who had complete response to methotrexate (MTX) after progressing on multiple cytotoxic agents, cetuximab, and AMG-479 (monoclonal antibody against insulin-like growth factor-1 receptor [IGF-1R]).


The clinical information was collected by a retrospective medical record review under an Institutional Review Board-approved protocol. From 4 tumors and 2 normal mucosal epithelia, global gene expression, and IGF-1R and dihydrofolate reductase (DHFR) protein levels were determined.


Effective target inhibition in the tumor was confirmed by the decreased protein levels of total and phospho-IGF-1R after treatment with AMG-479. Decreased level of DHFR and conversion of a gene expression profile associated with cetuximab-resistance to cetuximab-sensitivity were also observed.


This suggests that the combination of AMG-479 and MTX or cetuximab may be a promising therapeutic approach in refractory HNSCC.

Copyright © 2010 Wiley Periodicals, Inc.

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