Inhibitors of epidermal-growth-factor receptors: a review of clinical research with a focus on non-small-cell lung cancer - 28/08/11

Doi : 10.1016/S1470-2045(03)01137-9

Srikala S Sridhar ^a, Lesley Seymour ^c, Frances A Shepherd ^b,^⁎

^a Clinical Research Fellow in Medical Oncology, Division of Medical Oncology, Department of Medicine of the University Health Network, Princess Margaret Hospital and the University of Toronto

^b Professor of Medicine, Division of Medical Oncology, Department of Medicine of the University Health Network, Princess Margaret Hospital and the University of Toronto

^c co-ordinator of the Investigational New Drug Program of the National Cancer Institute of Canada Clinical Trials Group and Queen’s University, Ontario, Canada

^* Correspondence: Dr Frances A Shepherd, Princess Margaret Hospital, Suite 5104, 610 University Avenue, Toronto, ON, M5G 2M9. Tel: +1 416 946 4522. Fax: +1 416 416 6546

Summary

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, MDX447, 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).

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