TITLE:
ErbB Receptors and ErbB Targeted Therapies in Endometrial Cancer
AUTHORS:
Georgios Androutsopoulos, Georgios Michail, Georgios Adonakis, Georgios Decavalas
KEYWORDS:
Endometrial Cancer, ErbB Receptors, ErbB Targeted Therapy
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.5 No.6,
May
8,
2014
ABSTRACT: The Epidermal Growth
Factor system is present in human organs and plays an important role in cell
proliferation, differentiation and apoptosis during embryogenesis and postnatal
development. It has four receptors (EGFR, ErbB-2, ErbB-3 and ErbB-4) and
numerous ligands. Dysregulation of the Epidermal Growth Factor signaling
network is implicated in the pathogenesis of various disorders. Especially in cancer,
the Epidermal Growth Factor system becomes hyperactivated with various
mechanisms (ligand overproduction, receptor overproduction, constitutive
receptor activation). EGFR overexpression may have a dual role in endometrial
cancer. It seems that in type I endometrial cancer, EGFR overexpression did not
affect disease progression. However in type II endometrial cancer, EGFR
overexpression associated with high grade disease and adverse clinical outcome.
Moreover ΕrbB-2 overexpression especially in type II endometrial cancer, is an
indicator of a highly aggressive disease with poor overall survival. The
potential role of ErbB receptors (especially EGFR and ErbB-2) as targets for
cancer therapy has been investigated for over 20 years. There are 2 major classes
of ErbB targeted therapies: anti-ErbB monoclonal antibodies (MoAbs) and
ErbB-specific tyrosine kinase inhibitors (TKIs). ErbB targeted therapies have
still shown modest effect in unselected endometrial cancer patients. However,
they may be clinically active as adjuvant therapy in well-defined subgroups of
type II endometrial cancer patients with EGFR and ErbB-2 overexpression.