05.02.2 Receptors

Polymorphisms are not always associated with loss of activity. This is shown in the example of the receptor polymorphism; epidermal growth factor receptors. Epidermal growth factor receptors (EGFR) are from the receptor tyrosine kinase (TK) family. EGFR are overexpressed in many cancers, and promote the growth of the cancer (Figure 5.3).

Figure 5.3 Epidermal growth factor receptor (R) and tyrosine kinase (TK) (Copyright QUT, Sheila Doggrell)

Gefitinib inhibits EGFR-tyrosine kinase, and is used in the treatment of some cancers. There is a subset of patients who respond very well (and much better than most patients) to gefitinib. This subset of patients has a polymorphism in their EGFR-tyrosine kinase. Gefitinib is a more potent inhibitor of the polymorphism than the wild-type (normal) EGFR-tyrosine kinase. Thus, there is a better response to gefitinib in patients with this polymorphism.