Molecular approaches to receptors as targets for drug discovery

Many receptors have been selected as viable drug discovery targets. One particular class of receptors that have received much interest and so far relatively good success are the receptor protein tyrosine kinases (RPTKs). Typically, RPTKs are activated following the binding of the peptide growth factor ligand to its receptor. The RPTKs play crucial roles in signal transduction pathways that regulate a number of cellular functions, such as cell differentiation and proliferation, both under normal physiological conditions as well as in a variety of pathological disorders. A variety of different tumour types have been shown to have dysfunctional RPTKs, either as a result of excess production of the growth factor, the receptor or both, or via mutations in the RPTKs structure. Irrespective of the cause, this leads to the over-activity of the particular RPTK system and in turn to the aberrant and inappropriate cellular signalling within the tumour cell. RPTKs are attractive targets in the search for therapeutic agents, not only against cancers but also against many other disease indications. Although an ever-increasing number of RPTKs have been selected as viable molecular targets for drug discovery programmes, four examples will be covered in this article. These are the epidermal growth factor receptor (EGF-R), platelet-derived growth factor receptor (PDGF-R), fibroblast growth factor receptor (FGR-R) and vascular endothelial growth factor receptor (VEGF-R), with the main emphasis of interest being on their role in oncology.