Effector mechanisms of therapeutic antibodies against ErbB receptors.
ErbB1 and ErbB2 constitute validated target antigens for tumor therapy-as documented by the approval of antibodies and tyrosine kinase inhibitors (TKIs) against both antigens. However, their complex biology in development and tumorigenesis poses significant challenges on the optimization of this targeted approach. Crystallographic studies have significantly improved concepts about structure/function relationships of these receptors, and may assist in improving the efficacy of ErbB-directed therapy over the following years. Here, we will review these recent advances and their implications for ErbB-directed therapies. Although we will focus on the mechanisms of action of ErbB therapeutic antibodies, we will also briefly discuss TKIs.
Peipp
Matthias
M
Division of Stem Cell Transplantation and Immunotherapy, Christian-Albrechts-University, Schittenhelmstr. 12, Kiel, Germany.
Dechant
Michael
M
Valerius
Thomas
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use; D000068818:Cetuximab; D019281:Dimerization; D004791:Enzyme Inhibitors / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use; D066246:ErbB Receptors / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology; D018739:Oncogene Proteins v-erbB / Q000378:metabolism; D000077544:Panitumumab; D017434:Protein Structure, Tertiary; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000068818:Cetuximab; D004791:Enzyme Inhibitors; D066246:ErbB Receptors; D018739:Oncogene Proteins v-erbB; D000077544:Panitumumab; D020794:Receptor Protein-Tyrosine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab