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Head Neck. 2013 Sep;35(9):1323-30. doi: 10.1002/hed.23128. Epub 2012 Aug 21.

Effect of erlotinib on epidermal growth factor receptor and downstream signaling in oral cavity squamous cell carcinoma.

Author information

1
Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA. ctsien@umich.edu

Abstract

BACKGROUND:

The purpose of this study was to determine if there are differences in biomarker modulation and epidermal growth factor receptor (EGFR) degradation between the tumor and the normal mucosa after treatment with an EGFR inhibitor, erlotinib, in head and neck cancer.

METHODS:

Patients with primary oral cavity squamous cell cancers received a course of erlotinib, 150 mg every day for 7 days before surgical resection. Tumor and normal mucosa biopsies were obtained both pre-erlotinib and post-erlotinib. Changes in known markers of EGFR activity (phospho, AKT, STAT3) were measured by immunoblotting, whereas changes in tissue distribution were analyzed by immunohistochemical analysis.

RESULTS:

Twelve patients were enrolled; 7 had evaluable paired tumors and normal mucosa biopsies pretreatment and posttreatment. Expression of EGFR was higher in tumors compared to the normal mucosa (p = .005). Erlotinib administration was associated with marked inhibition of phosphorylated epidermal growth factor receptor (pEGFR) and reduction in total EGFR protein (p = .004, p = .007) in tumors, whereas there was heterogeneity in EGFR inhibition in the normal mucosa (p = .10 [pEGFR], and p = .07 [EGFR]). Reduced levels of pSrc and pSTAT3 and enhanced p27 levels were noted in tumors after erlotinib. Cell culture studies confirmed that EGFR is degraded in tumor cells after prolonged treatment with erlotinib.

CONCLUSION:

Our results show that EGFR inhibition by erlotinib led to a marked reduction in EGFR protein levels in patients. Differential effects of erlotinib on tumors compared to the normal mucosa suggest there may be individual patient heterogeneity. These preliminary data suggest EGFR degradation should be further analyzed as a potential biomarker in selecting patients likely to benefit from EGFR inhibitors.

KEYWORDS:

biomarker; degradation; erlotinib; normal mucosa; primary oral cavity cancer

PMID:
22907806
PMCID:
PMC4364542
DOI:
10.1002/hed.23128
[Indexed for MEDLINE]
Free PMC Article

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