Type I growth factor receptors: current status and future work.

The type 1 family of growth factor receptors consists of the epidermal growth factor receptor (EGFR), and ErbB-2, ErbB-3 and ErbB-4. Six ligands are known to bind directly to EGFR, none (at present) to ErbB-2, and a family of ligands collectively called the neuregulins bind to both ErbB-3 and ErbB-4. It is now apparent that the receptors function in various heterodimeric pairs, depending on their concentrations, the concentrations of particular ligands in the environment and some intrinsic degree of dimer selectivity. Overexpression of EGFR, ErbB-2 and ErbB-3 has been found commonly in solid human tumours. ErbB-4 has not yet been examined. The EGFR is also activated by various mutations in brain tumours and possibly in other tumour types. These changes appear to be one of the causes of malignant transformation. They may also provide information regarding the course of disease and response to current treatments. Finally, they are targets for a variety of new forms of treatment being developed in the laboratory, in preclinical models and in a few cases in clinical trials.