, Volume 2, Issue 2, pp 73-88

Targeted therapies in head and neck cancer

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Abstract

Over the past decade, the important role of different growth factors and their receptors and signal transduction pathways in the genesis and progression of tumors has been well recognized and their mechanism of action and interactions is gradually being unraveled. Epidermal growth factor receptor (EGFR) overexpression is present in the vast majority of squamous cell head and neck cancers and carries a worse prognosis. EGFR is the target of multiple specifically targeted monoclonal antibodies and tyrosine kinases, which are in various stages of clinical development in squamous cell carcinoma of the head and neck (SCCHN). The search for EGFR mutations is an area of active investigation. The incidence and impact of EGFR mutations in SCCHN has yet to be determined. EGFR downstream signaling pathways are the target of farnesyltransferase inhibitors (FTIs) and mammalian target of rapamycin (mTOR) inhibitors. Cyclooxygenase-2 (COX-2) is overexpressed in premalignant lesions (oral leukoplakia) and in squamous cell carcinoma of the head and neck. EGFR and COX-2 signaling pathways form a positive feedback loop. As their toxicity profiles are non-overlapping, combination of COX-2 inhibitors and EGFR targeted therapies looks attractive. The majority of the studies, although not all, examining the prognostic significance of vascular endothelial growth factor (VEGF) expressing did observe a worse outcome in patients with SCCHN expressing VEGF and VEGF receptor 2 (VEGFR-2). Anti-VEGF strategies include neutralizing antibodies to VEGF or VEGFR and VEGFR tyrosine kinase inhibitors. Aurora kinase inhibitors, insulin like growth factor inhibitors, and histone acetylase inhibitors have recently gained interest as potential new promising ways of tackling tumors including SCCHN.