TAILIEUCHUNG - Báo cáo khoa học: Epidermal growth factor receptor in relation to tumor development: EGFR-targeted anticancer therapy

The discovery that signaling by the epidermal growth factor receptor (EGFR) plays a key role in tumorigenesis prompted efforts to target this receptor in anticancer therapy. Two different types of EGFR-targeted ther-apeutic agents were subsequently developed: mAbs, such as cetuximab and panitumumab, which target the extracellular domain of the receptor, | ỊFEBS Journal MINIREVIEW Epidermal growth factor receptor in relation to tumor development EGFR-targeted anticancer therapy Isamu Okamoto Department of MedicalOncology Kinki University Schoolof Medicine Osaka Japan Keywords epidermalgrowth factor receptor EGFR mutation KRAS mutation monoclonal antibodies tyrosine kinase inhibitor Correspondence I. Okamoto Department of Medical Oncology Kinki University Schoolof Medicine 377-2 Ohno-higashi Osaka-Sayama Osaka 589-8511 Japan Tel 81 72 366 0221 Fax 81 72 360 5000 E-mail chi-okamoto@ Received 17 July 2009 revised 26 September 2009 accepted 8 October 2009 doi The discovery that signaling by the epidermal growth factor receptor EGFR plays a key role in tumorigenesis prompted efforts to target this receptor in anticancer therapy. Two different types of EGFR-targeted therapeutic agents were subsequently developed mAbs such as cetuximab and panitumumab which target the extracellular domain of the receptor thereby inhibiting ligand-dependent EGFR signal transduction and smallmolecule tyrosine kinase inhibitors such as gefitinib and erlotinib which target the intracellular tyrosine kinase domain of the EGFR. Furthermore recent clinical and laboratory studies have identified molecular markers that have the potential to improve the clinical effectiveness of EGFR-targeted therapies. This minireview summarizes the emerging role of molecular profiling in guiding the clinical use of anti-EGFR therapeutic agents. KRAS mutations and sensitivity to therapy with mAb to epidermal growth factor receptor in colorectal cancer Cetuximab is a chimeric mouse-human mAb that targets the extracellular domain of the epidermal growth factor receptor EGFR and thereby blocks downstream signal transduction via the phosphatidylinositol 3-kina-se Akt and Ras Raf mitogen-activated protein kinase pathways Fig. 1 . Because it is an antibody IgG1 isotype cetuximab may also induce antibody-dependent .

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