Model tumor specific splice variant: EGFRvIII, a novel form of the EGF receptor

The EGF receptor has been shown to be essential for the growth of multiple human tumors. Numerous studies have validated it as a critical target for drug development. Several compounds that specifically disable the EGF receptor are now under development including small molecule tyrosine kinase inhibitors or monoclonal antibodies. One such drug, Iressa, has already been approved by the FDA. Yet the EGF receptor is present on many normal tissues in the body and in some organs, the liver for example, the amounts of receptor are comparable to that found in tumors. EGFRvIII is a naturally occurring variant form of the EGF receptor that was discovered by Dr. Albert Wong. It is the result of exon 1 joining to exon 8 in the EGF receptor gene. Studies by Dr. Wong and others have shown that it is constitutively active and oncogenic. More importantly, it is expressed in many types of human tumors but only rarely found in normal tissues. The fact that it is tumor specific and contributes to the formation of tumors makes it a superb target. Indeed, several preclinical studies have now validated EGFRvIII as a therapeutic target.