The ErbB family consists of four closely related tyrosine kinase receptors that act as potent mediators of normal cell growth and development. Aberrant expression or function of one or more of these receptors can play a major role in the development and evolution of cancer. ErbB-2, also known as HER2, has been implicated in the evolution of both breast and gastric cancers, and is evident in other cancer types such as ovarian and salivary gland tumors. ErbB-2 possesses an active tyrosine kinase domain, but no direct ligand has been identified yet. ErbB-2 is the preferred binding partner to the other members of the ErbB family and is thought to act primarily through the Ras-MAPK, PI3k-PKB/Akt, and PLC-PKC signaling pathways. Numerous anti-cancer strategies have been employed against erbB-2, such as antibody-based therapies to prevent ligand binding or receptor activation through dimerization, antibody-dependent cell mediated cytotoxicity, in addition to direct kinase inhibition to prevent molecular activation/downstream signaling.
