The epidermal growth factor receptor: from mutant oncogene in nonhuman cancers to therapeutic target in human neoplasia.

摘要: Approximately two decades ago, the epidermal growth factor receptor (EGFR) was discovered to be proto-oncogene of mutant, constitutively active oncogenic v-erbB tyrosine kinase, which induces avian erythroblastosis. Unlike mutant oncogene, EGFR requires activation by binding ligand its extracellular (EC) domain, whereas cellular effects depend on cytoplasmic kinase. The overexpression and ligands in several human carcinomas their association with accelerated tumor progression provided a rationale for targeting this network tumor-selective strategies. Two those antireceptor approaches, both solidly based known structure function EGFR, are discussed. first strategy involves development humanized monoclonal antibodies against nonconserved receptor's EC domain. These block can induce endocytosis downregulation. second approach is generation ATP mimetics that compete kinase pocket, thus disabling signal transduction. Preclinical early clinical studies already suggest these either alone or combination standard anticancer therapies, will able alter natural history EGFR-expressing cancers little no toxicity tumor-bearing host.