title: Targeting erbB receptors.
abstract: Our work is concerned with the origins and therapy of human cancers. Members of the epidermal growth factor receptor (EGFR) family of tyrosine kinases, also known as erbB or HER receptors, are over expressed and/or activated in many types of human tumors and represent important therapeutic targets in cancer therapy. Studies from our laboratory identified targeted therapy as a way to treat cancer. Rational therapeutics targeting and disabling erbB receptors have been developed to reverse the malignant properties of tumors. Reversal of the malignant phenotype, best seen with disabling the HER2 receptors using monoclonal antibodies is a distinct process from that seen with blocking of ligand binding to cognate receptors as has been done for EGFr receptors. Here we review the mechanisms of action deduced from a number of approaches developed in our laboratory and elsewhere, including monoclonal antibodies, peptide mimetics, recombinant proteins and small molecules. The biochemical and biological principles which have been uncovered during these studies of disabling HER2 homomeric or HER2-EGFr heteromeric receptors will help the development of novel and more efficient therapeutics targeting erbB family receptors.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104-6082, USA.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Cai
authors.forename: Hongtao
authors.initials: H
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Alan
authors.initials: A
authors.lastname: Berezov
authors.forename: Ramachandran
authors.initials: R
authors.lastname: Murali
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.forename: Mark I
authors.initials: MI
authors.lastname: Greene
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D066246:ErbB Receptors