Targeting epidermal growth factor receptor and SRC pathways in head and neck cancer.
Epidermal growth factor receptor (EGFR), a member of the ErbB family of receptor tyrosine kinases (RTKs), is highly expressed in head and neck squamous cell carcinoma (HNSCC) where increased EGFR expression levels in tumors are associated with decreased survival. HNSCC patient responses to EGFR-targeted monotherapies in clinical trials, though significant, have been limited. Tumor signaling pathway components that work in cooperation with EGFR or provide compensation for the loss of EGFR-initiated signaling will be ideal targets for therapies to be used in combination with EGFR-targeted agents. Based on the current understanding of molecular signaling pathways and available agents, ErbB family-targeted and Src family-targeted agents represent strategies for further exploration. Here, we discuss agents targeting ErbB and Src family kinases in clinical development, provide an overview of completed and ongoing clinical trials, and outline a molecular rationale for combining ErbB- and Src-targeted therapeutics.
Department of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
Ann Marie
AM
Egloff
Jennifer R
JR
Grandis
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy; D002986:Clinical Trials as Topic; D016503:Drug Delivery Systems / Q000379:methods*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000276:immunology; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D008954:Models, Biological; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000037:antagonists & inhibitors*; D015398:Signal Transduction
D000911:Antibodies, Monoclonal; D066246:ErbB Receptors; D016392:Proto-Oncogene Proteins pp60(c-src)