Mechanism of action of trastuzumab and scientific update.
The humanized anti-p185(HER2) monoclonal antibody trastuzumab has been shown to effectively inhibit the growth of HER2-overexpressing breast cancer cells in vivo and in vitro. The treatment of cancer cells with trastuzumab results in downregulation of the HER2 receptor. Further downstream cellular events include the accumulation of the cyclin-dependent kinase inhibitor p27 and cell cycle arrest. In vivo, trastuzumab induces antibody-dependent cellular cytotoxicity. Trastuzumab also inhibits constitutive HER2 cleavage/shedding mediated by metalloproteases. The ability of trastuzumab to inhibit HER2 cleavage may correlate with the clinical anticancer activity of the multifunctional HER2-targeting antibody.
Baselga
J
J
Medical Oncology Service, Vall D'Hebron University Hospital, Barcelona, Spain.
Albanell
J
J
Molina
M A
MA
Arribas
J
J
D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000187:drug effects; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D017452:Receptors, IgG; D000068878:Trastuzumab; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases; D004791:Enzyme Inhibitors; D011505:Protein-Tyrosine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D017452:Receptors, IgG; D000068878:Trastuzumab; D025521:Tumor Suppressor Proteins