Improving Response Rates to EGFR-Targeted Therapies for Head and Neck Squamous Cell Carcinoma: Candidate Predictive Biomarkers and Combination Treatment with Src Inhibitors

被引:46
作者
Egloff, Ann Marie [1 ]
Grandis, Jennifer Rubin [1 ,2 ,3 ]
机构
[1] Univ Pittsburgh, Dept Otolaryngol, Pittsburgh, PA 15213 USA
[2] Univ Pittsburgh, Dept Pharmacol, Pittsburgh, PA 15213 USA
[3] Eye & Ear Inst, Pittsburgh, PA 15213 USA
关键词
D O I
10.1155/2009/896407
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The epidermal growth factor receptor- (EGFR-) directed antibody, cetuximab, was FDA-approved for the treatment of squamous cell carcinoma of the head and neck (SCCHN) in 2006. Additional EGFR-targeting agents in clinical development for SCCHN include other EGFR-directed antibodies, tyrosine kinase inhibitors and antisense DNA. Although the majority of SCCHN overexpress EGFR, SCCHN clinical responses to EGFR-targeting agents have been modest. Molecular predictors for SCCHN response to EGFR-targeted therapies have not been identified. However, molecular correlate studies in lung cancer and colon cancer, which have EGFR-targeted therapeutics FDA-approved for treatment, may provide insights. We describe candidate predictive markers for SCCHN response to EGFR-targeted therapies and their prevalence in SCCHN. Clinical response will likely be improved by targeted therapy combination treatments. Src family kinases mediate EGFR-dependent and -independent tumor progression pathways in many cancers including SCCHN. Several Src-targeting agents are in clinical development for solid malignancies. Molecular correlate studies for Src-targeting therapies are few and biomarkers correlated with patient response are limited. Identifying SCCHN patients who will respond to combined EGFR-and Src-targeting will require further characterization of molecular correlates. We discuss rationale for EGFR and Src co-targeting for SCCHN treatment and describe recent clinical trials implementing combined Src-and EGFR-targeted therapeutics. Copyright (C) 2009 A. M. Egloff and J. R. Grandis.
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页数:12
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共 92 条
[91]   Src family kinases mediate epidermal growth factor receptor ligand cleavage, proliferation, and invasion of head and neck cancer cells [J].
Zhang, Q ;
Thomas, SM ;
Xi, SC ;
Smithgall, TE ;
Siegfried, JM ;
Kamens, J ;
Gooding, WE ;
Grandis, JR .
CANCER RESEARCH, 2004, 64 (17) :6166-6173
[92]   Phosphorylation of TNF-α converting enzyme by gastrin-releasing peptide induces amphiregulin release and EGF receptor activation [J].
Zhang, Q ;
Thomas, SM ;
Lui, VWY ;
Xi, S ;
Siegfried, JM ;
Fan, H ;
Smithgall, TE ;
Mills, GB ;
Grandis, JR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (18) :6901-6906