Inhibitors of epidermal-growth-factor receptors: a review of clinical research with a focus on non-small-cell lung cancer.
Despite aggressive surgical and chemotherapeutic interventions, non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related death in men and women with overall cure rates of less than 15%. Recent advances in our understanding of cellular signalling and its critical role in tumorigenesis has led to the development of novel therapies which may offer new hope. In particular, the epidermal growth-factor receptor superfamily is an attractive therapeutic target because it is commonly overexpressed in malignant disease, regulates many vital cellular processes, and seems to be a negative prognostic indicator. Several selective inhibitors of this family of receptors are currently being evaluated in several cancers including NSCLC. In this review we examine current preclinical and clinical evidence on monoclonal antibodies (cetuximab, ABX-EGF, EMD72000, MAb ICR62, h-R3, MDX-447, MDX-H210, trastuzumab, and 2C4), immunoconjugates (Y10, Ua30:2, Mab806), anti-EGF vaccine (YMB2000), and tyrosine kinase inhibitors (gefitinib, erlotinib, CI1033, GW572016, EKB 569, PKI166, PD158780, and TAK 165).
Sridhar
Srikala S
SS
Division of Medical Oncology, Department of Medicine of the University Health Network, Princess Margaret Hospital and the University of Toronto, Canada.
Seymour
Lesley
L
Shepherd
Frances A
FA
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D000068818:Cetuximab; D002986:Clinical Trials as Topic; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011799:Quinazolines / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D015996:Survival Rate
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C000603968:ICR62 monoclonal antibody; D011799:Quinazolines; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D000068818:Cetuximab; D000077156:Gefitinib