Receptor tyrosine kinases as therapeutic targets in cancer.

Extract: Tyrosine kinases are a large and diverse family of proteins found only in Metazoans. The ERBB receptor tyrosine kinases (RTK), the main focus of this article, belong to the sub-group encompassing the cell surface proteins. All receptor tyrosine kinases have an extracellular domain that binds peptide ligands, span the membrane once, and have an intracellular portion with protein tyrosine kinase activity. Ligand binding to receptor tyrosine kinases induces the formation of receptor dimers and activates the kinase domain of the receptor, which transfers a phosphate group from the bound ATP to specific tyrosine side chains on the receptor proteins and on intracellular signaling proteins that bind the active receptor tyrosine kinases. In many types of human tumors, ERBB (erythroblastosis group B) receptor tyrosine kinases are aberrantly activated and contribute to cancer development. Accordingly, these receptors have been intensely studied both to understand their roles in cancer biology and to employ them as therapeutic targets. Many ERBB targeted inhibitors are now in clinical use.