ErbB Receptors and ErbB Targeted Therapies in Endometrial Cancer

Abstract

The Epidermal Growth\rFactor system is present in human organs and plays an important role in cell\rproliferation, differentiation and apoptosis during embryogenesis and postnatal\rdevelopment. It has four receptors (EGFR, ErbB-2, ErbB-3 and ErbB-4) and\rnumerous ligands. Dysregulation of the Epidermal Growth Factor signaling\rnetwork is implicated in the pathogenesis of various disorders. Especially in cancer,\rthe Epidermal Growth Factor system becomes hyperactivated with various\rmechanisms (ligand overproduction, receptor overproduction, constitutive\rreceptor activation). EGFR overexpression may have a dual role in endometrial\rcancer. It seems that in type I endometrial cancer, EGFR overexpression did not\raffect disease progression. However in type II endometrial cancer, EGFR\roverexpression associated with high grade disease and adverse clinical outcome.\rMoreover ΕrbB-2 overexpression especially in type II endometrial cancer, is an\rindicator of a highly aggressive disease with poor overall survival. The\rpotential role of ErbB receptors (especially EGFR and ErbB-2) as targets for\rcancer therapy has been investigated for over 20 years. There are 2 major classes\rof ErbB targeted therapies: anti-ErbB monoclonal antibodies (MoAbs) and\rErbB-specific tyrosine kinase inhibitors (TKIs). ErbB targeted therapies have\rstill shown modest effect in unselected endometrial cancer patients. However,\rthey may be clinically active as adjuvant therapy in well-defined subgroups of\rtype II endometrial cancer patients with EGFR and ErbB-2 overexpression.