The epidermal growth factor receptor–tyrosine kinase: A promising therapeutic target in solid tumors

摘要: Abstract The overexpression and aberrant function of the epidermal growth factor receptor (EGFR) its ligands in several human carcinomas have provided a rationale for targeting this signaling network with novel treatment approaches. receptor–tyrosine kinase (EGFR-TK) is selective target inhibiting cancer because it activated many tumor cells, yet strictly controlled normal cells. EGFR-TK initiates diverse signal transduction pathways cells that profound effect on their biology. Activation provides signals drive dysregulated proliferation, invasion metastasis, angiogenesis, enhanced cell survival. Therefore, promising drug types solid tumors, inhibition has potential both prevention these neoplasias. Based structure EGFR, two antireceptor therapeutic strategies been developed. first strategy uses humanized monoclonal antibodies generated against receptor's ligand-binding, extracellular domain. These block binding receptor-activating and, some cases, can induce endocytosis downregulation. second approach small molecules compete adenosine triphosphate to pocket, thus blocking activation postreceptor signals. Early clinical studies suggest approaches, either alone or combination standard anticancer therapies, are well tolerated responses stabilization variety common carcinomas. ZD1839 (Iressa; AstraZeneca Pharmaceuticals LP, Wilmington, DE) inhibitor furthest along development, currently being investigated including non–small-cell lung cancer. Semin Oncol 30 (suppl 1):3-11. Copyright 2003, Elsevier Science (USA). All rights reserved.