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

Christine H. Chung; Paula R. Pohlmann; MacE L. Rothenberg; Brian B. Burkey; Joel Parker; Kevin Palka; Joseph Aulino; Igor Puzanov; Barbara Murphy

doi:10.1002/hed.21478

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

Christine H. Chung, Paula R. Pohlmann, MacE L. Rothenberg, Brian B. Burkey, Joel Parker, Kevin Palka, Joseph Aulino, Igor Puzanov, Barbara Murphy

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	1804-1808
Number of pages	5
Journal	Head and Neck
Volume	33
Issue number	12
DOIs	https://doi.org/10.1002/hed.21478
State	Published - Dec 2011
Externally published	Yes

Keywords

AMG-479
cetuximab
head and neck squamous cell carcinoma
IGF-1R inhibitor
methotrexate

ASJC Scopus subject areas

Otorhinolaryngology

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10.1002/hed.21478

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

abstract = "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.",

keywords = "AMG-479, cetuximab, head and neck squamous cell carcinoma, IGF-1R inhibitor, methotrexate",

author = "Chung, {Christine H.} and Pohlmann, {Paula R.} and Rothenberg, {MacE L.} and Burkey, {Brian B.} and Joel Parker and Kevin Palka and Joseph Aulino and Igor Puzanov and Barbara Murphy",

year = "2011",

month = dec,

doi = "10.1002/hed.21478",

language = "English (US)",

volume = "33",

pages = "1804--1808",

journal = "Head and Neck",

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T1 - Insulin-like growth factor-1 receptor inhibitor, AMG-479, in cetuximab-refractory head and neck squamous cell carcinoma

AU - Chung, Christine H.

AU - Pohlmann, Paula R.

AU - Rothenberg, MacE L.

AU - Burkey, Brian B.

AU - Parker, Joel

AU - Palka, Kevin

AU - Aulino, Joseph

AU - Puzanov, Igor

AU - Murphy, Barbara

PY - 2011/12

Y1 - 2011/12

N2 - 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.

AB - 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.

KW - AMG-479

KW - cetuximab

KW - head and neck squamous cell carcinoma

KW - IGF-1R inhibitor

KW - methotrexate

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

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