Combined inhibition of c-Src and epidermal growth factor receptor abrogates growth and invasion of head and neck squamous cell carcinoma

Priya Koppikar, Seung Ho Choi, Ann Marie Egloff, Quan Cai, Shinsuke Suzuki, Maria Freilino, Hiroshi Nozawa, Sufi M. Thomas, William E. Gooding, Jill M. Siegfried, Jennifer R. Grandis

Research output: Contribution to journalArticlepeer-review

90 Scopus citations

Abstract

Purpose: Increased expression and/or activation of epidermal growth factor receptor (EGFR) is associated with tumor progression and poor prognosis in many cancers, including head and neck squamous cell carcinoma (HNSCC). Src family kinases, including c-Src, mediate a variety of intracellular or extracellular signals that contribute to tumor formation and progression. This study was undertaken to elucidate the role of c-Src in the growth and invasion of HNSCC and to determine the effects of combined targeting of EGFR and Src kinases in HNSCC cell lines. Experimental Design: HNSCC ceils were engineered to stably express a dominant-active form of c-Src and investigated in cell growth and invasion assays. The biochemical effects of combined treatment with the Src inhibitor AZD0530, a potent, orally active Src inhibitor with Bcr/Abl activity, and the EGFR kinase inhibitor gefitinib were examined, as well as the consequences of dual Src/EGFR targeting on the growth and invasion of a panel of HNSCC cell lines. Results: HNSCC cells expressing dominant-active c-Src showed increased growth and invasion compared with vector-transfected controls. Combined treatment with AZD0530 and gefitinib resulted in greater inhibition of HNSCC cell growth and invasion compared with either agent alone. Conclusions: These results suggest that increased expression and activation of c-Src promotes HNSCC progression where combined targeting of EGFR and c-Src may be an efficacious treatment approach.

Original languageEnglish (US)
Pages (from-to)4284-4291
Number of pages8
JournalClinical Cancer Research
Volume14
Issue number13
DOIs
StatePublished - Jul 1 2008
Externally publishedYes

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