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

Chung CH, Pohlmann PR, Rothenberg ML, Burkey BB, Parker J, Palka K, Aulino J, Puzanov I, Murphy B
Head Neck. 2011 33 (12): 1804-8

PMID: 20652976 · PMCID: PMC3111896 · DOI:10.1002/hed.21478

BACKGROUND - 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]).

METHODS - 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.

RESULTS - 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.

CONCLUSION - 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.

MeSH Terms (11)

Antibodies, Monoclonal Antibodies, Monoclonal, Humanized Antineoplastic Agents Carcinoma, Squamous Cell Cetuximab Female Head and Neck Neoplasms Humans Methotrexate Middle Aged Receptor, IGF Type 1

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