Mutations of EGFR in lung cancers and their implications for targeted therapy.
Extract: The epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases [enzymes which phosphorylate (add phosphate groups to) tyrosine residues in proteins] is dysregulated in many human cancers and plays important roles in their development and progression. The family has four member molecules: ERBB1/EGFR/HER1 (located on chromosome 7), ERBB2/HER2 (on chromosome 17), ERBB3/ HER3 (on chromosome 12) and ERBB4/HER4 (on chromosome 2). These receptor molecules are composed of an extracellular ligand-binding domain, a transmembrane segment and an intracellular tyrosine kinase domain followed by a regulatory segment. Although tyrosine kinase domains of the family members are highly homologous to each other, they have distinct properties. The binding of a ligand (a small molecule that binds to a receptor) to its specific receptor results in autophosphorylation of specific tyrosine residues of the receptor and triggers the activation of several important downstream signaling pathways. EGFR and HER2 have been widely studied in many human cancers. Overexpression of EGFR is frequently observed in several human cancers, and gene variants (EGFRvIII) (i.e., increased expression and/or proteins with different amino acid sequences, and potentially different reactivity or even functions) are frequently found in glioblastomas (a form of brain tumor). Over-expression of HER2 is found in a subset of breast and ovarian cancers correlating with poor prognosis.
Shigematsu
Hisayuki
H
Hamon Center for Therapeutic Oncology Research and the Department of Pathology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
Gazdar
Adi F
AF