Anticancer therapy targeting the erbB family of receptor tyrosine kinases.
Several agents that target one or more members of the erbB family of receptor tyrosine kinases are currently undergoing clinical investigation. The monoclonal antibody trastuzumab has been shown effective in erbB2-expressing metastatic breast cancer when administered as a single agent or in combination with cytotoxic chemotherapy. Toxicities associated with trastuzumab include infusion-related fever and chills, hypersensitivity reactions, and congestive heart failure. C225 is a monoclonal antibody directed against the epidermal growth factor receptor, which has shown encouraging antitumor activity in early clinical development. The orally active tyrosine kinase inhibitors show encouraging antitumor activity in preclinical models and early clinical trials. Members of this class currently in clinical development include ZD1839, OSI-774, and CI-1033. Evidence to date suggests that the major role for erbB receptor-targeting drugs will be in combined therapy to enhance response to cytotoxic drugs, and in long-term monotherapy to maintain response and prevent disease progression or recurrence.
Slichenmyer
W J
WJ
Departments of Oncology Clinical Development and Cancer Research, Pfizer Global Research and Development, Ann Arbor, MI 48105, USA.
Fry
D W
DW
D000818:Animals; D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism; D000068818:Cetuximab; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D000069347:Erlotinib Hydrochloride; D000077156:Gefitinib; D006801:Humans; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000627:therapeutic use; D011758:Pyrroles / Q000627:therapeutic use; D011799:Quinazolines / Q000627:therapeutic use; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors; D000068878:Trastuzumab
D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000068818:Cetuximab; D004791:Enzyme Inhibitors; D066246:ErbB Receptors; D000069347:Erlotinib Hydrochloride; D000077156:Gefitinib; D011505:Protein-Tyrosine Kinases; D011743:Pyrimidines; D011758:Pyrroles; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C121360:MDX-H210 antibody; C410026:PKI 166