Role of ErbB family receptor tyrosine kinases in intrahepatic cholangiocarcinoma

摘要: Aberrant expression and signaling of epidermal growth factor receptor (ErbB) family tyrosine kinases, most notably that ErbB2 ErbB1, have been implicated in the molecular pathogenesis intrahepatic cholangiocarcinoma. Constitutive overexpression and/or ErbB1 malignant cholangiocytes has raised interest possibility agents which selectively target these receptors could potentially be effective cholangiocarcinoma therapy. However, current experience with such ErbB-directed therapies at best produced only modest responses patients biliary tract cancers. This review provides a comprehensive critical analysis both preclinical clinical studies aimed assessing role altered expression, genetic modifications, dysregulated on development progression. Specific limitations experimental approaches used to assess human specimens for gene amplification are discussed. In addition, rodent models cholangiocarcinogenesis associated constitutive reviewed. Select interactive relationships between or other relevant pathways progression also detailed, including those linking ErbB bile acid, cyclooxygenase-2, interleukin-6/gp130, transmembrane mucins, hepatocyte factor/Met, vascular endothelial signaling. Lastly, various factors can limit therapeutic efficacy ErbB-targeted against considered.