Epidermal growth factor receptor biology in head and neck cancer.
Epidermal growth factor receptor (EGFR) is overexpressed in several epithelial malignancies, including head and neck squamous cell carcinoma (HNSCC), which exhibits EGFR overexpression in up to 90% of tumors. EGFR ligands such as transforming growth factor alpha are also overexpressed in HNSCC. EGFR plays a critical role in HNSCC growth, invasion, metastasis and angiogenesis. However, EGFR inhibitors as monotherapy have yielded only modest clinical outcomes. Potential mechanisms for lack of response to EGFR inhibition in HNSCC include constitutive activation of signaling pathways independent of EGFR, as well as genetic aberrations causing dysregulation of the cell cycle. EGFR-directed therapy may be optimized by identifying and selecting those HNSCC patients most likely to benefit from EGFR inhibition. Resistance to EGFR inhibition may be circumvented by combination therapy employing EGFR inhibitors together with other treatment modalities.
Kalyankrishna
Shailaja
S
Department of Otolaryngology, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Grandis
Jennifer R
JR
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D009362:Neoplasm Metastasis; D018579:Patient Selection; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors