%0 Journal Article
%T Targeted therapy in NSCLC driven by HER2 insertions
%A Solange Peters
%A Stefan Zimmermann
%J SCIE-indexed Journal
%D 2014
%X Research into the molecular basis of lung cancer has revealed insights into various critical pathways that are deregulated, and among them, key driver genetic alterations that promote cell survival and proliferation. In the oncogene addiction model, cancer cells harbor gene amplification, rearrangement or mutations that dictate their malignant phenotype, and can thus be referred to as driver alterations (1). Among them, human epidermal growth factor 2 (HER2 erbB-2/neu) is a member of the erbB receptor tyrosine kinase family. The ERBB2 gene which encodes for HER2 is a major proliferative driver that activates downstream signaling through PI3K-AKT and MEK-ERK pathways (2). Unlike HER1/epidermal growth factor receptor (EGFR), HER2 has no known ligand, and is activated by homo-dimerization or hetero-dimerization with other members of the erbB family. Under resting conditions, these cell-surface receptors are found as monomers folded in a so-called ˇ°closedˇ± inactive conformation that prevents dimerization (3). Upon ligand binding to the extracellular domain, conformational rearrangements lead to an ˇ°openˇ± state that exposes the dimerization interface. This extracellular dimeric structure results in the transactivation of the intracellular tyrosine kinase portion of each receptor. Three principal mechanisms of oncogenic activation of HER2 have been described: HER2 gene amplification, gene mutation resulting in molecular alterations of the receptor or HER2 protein overexpression
%U http://tlcr.amegroups.com/article/view/2263/2886