title: ErbB receptor tyrosine kinase inhibitors as therapeutic agents.
abstract: The ErbB family of receptor tyrosine kinases comprise four members: EGFR, ErbB2, ErbB3 and ErbB4. All are essential for normal development and participate in the functioning of normal cells. ErbB receptors, particularly EGFR and ErbB2 are commonly deregulated in certain prevalent forms of human cancer. Recently a number of small molecule inhibitors of the tyrosine kinase activity of these receptors have been developed. Some of these agents, known as TKIs, are progressing through clinical trials in patients with aberrant ErbB receptor expression in their tumors. This article provides a brief overview on the structure and biology of ErbB receptors and their ligands before discussing in detail the development and current status of ErbB receptor TKIs. These agents are shown to inhibit multiple features of cancer cells including proliferation, survival, invasion and angiogenesis. It is clear from recent studies that not all cancer cells that overexpress ErbB receptors will be sensitive to TKIs. Potential explanations for resistance to these molecules are reviewed. Finally the prospect of using TKIs in combination with existing chemotherapeutic agents is discussed.
authors.affiliation: Division of Cancer Studies, School of Medicine, University of Manchester, Oxford Road, Manchester M13 9PT, United Kingdom. anderson@man.ac.uk
authors.forename: Neil G
authors.initials: NG
authors.lastname: Anderson
authors.forename: Tawhid
authors.initials: T
authors.lastname: Ahmad
mesh_terms: D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000188:drug therapy* / Q000209:etiology; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology; D020893:Receptor, ErbB-3 / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology; D066247:Receptor, ErbB-4; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D066247:Receptor, ErbB-4; C587689:ERBB4 protein, human