Aberrant kinase signaling: lessons from head and neck cancer.
Cancers, including head and neck squamous cell carcinoma (HNSCC), are characterized by the increased expression of receptor and nonreceptor tyrosine kinases. Many small molecules have been developed that selectively inhibit these kinases. These drugs have demonstrated antitumor effects in many preclinical cancer models and are now either approved for use in selected cancer patients or are under active clinical development. Receptor tyrosine kinases can also be targeted using monoclonal antibodies. Cetuximab is a chimeric antibody that inhibits the epidermal growth factor receptor and was approved for use in HNSCC, making it the first new drug for the treatment of this malignancy in over 40 years. Serine/threonine kinases are also aberrantly expressed in HNSCC and inhibitors of these kinases are being developed for clinical use. These developments will allow for the rational design of treatment regimens for HNSCC patients based on the aberrant kinase signaling in their tumors.
Nelson
Elizabeth G
EG
Department of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Grandis
Jennifer R
JR
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000068818:Cetuximab; D002986:Clinical Trials as Topic; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D066246:ErbB Receptors; D000068818:Cetuximab