Role of Receptor Tyrosine Kinases in Lung Cancer

Lung cancer cells express receptor tyrosine kinases (RTKs) that may be important targets for therapies. RTKs are proto-oncogenes, which are key regulators for cell growth, differentiation, survival, or motility. More than 50 RTKs, in both lung and other tissues, have been identified (1 ). The receptors contain an N-terminal extracellular ligand-binding domain, a single transmembrane α helix, and a cytosolic C-terminal domain with tyrosine kinase activity. The binding of growth factors to the RTKs extracellular domain activates the cytosolic kinase domain. Growth factor activation of the RTK results in dimerization of the receptor, with phosphorylation of the receptor and downstream targets. Upon activation of RTKs, various biological functions are altered in lung cancer cells, including cell growth, migration/motility, alterations of reactive oxygen species (ROS), and activation of downstream signal-transduction events.