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clinical implications of egfr expression in the development and progression of solid tumors- focus on nonsmall cell lung cancer.doc

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Clinical Implications of EGFR Expression in the Development and Progression of Solid Tumors: Focus on NonSmall Cell Lung Cancer 【关键词】nbsp; EGFR,amp;#8226;,Cancer,therapy,amp;#8226;,Lung,cancer,amp;#8226;,Anti-EGFR,agents 　　LEARNING OBJECTIVESnbsp; 　　After completing this course, the reader will be able to: 　　Describe the EGFR signaling pathway as a target for new anticancer agents. 　　Characterize the various EGFR agents developed for the treatment of NSCLC. 　　Identify the appropriate indications for the use of these new agents. 　　ABSTRACTnbsp; nbsp; 　　Dysregulation of the epidermal growth factor receptor (EGFR) signaling pathway is associated with the development and progression of malignancy, and EGFR-targeted therapies offer the promise of better treatment for many types of solid tumors, including non-small cell lung cancer. Anti-EGFR agents include monoclonal antibodies (mAbs) targeting the EGFR extracellular receptor domain and small-molecule tyrosine kinase inhibitors (TKIs) targeting the EGFR intracellular kinase domain. Both mAbs and TKIs have demonstrated encouraging results as monotherapies and in combination with chemotherapy and radiotherapy. This review provides a critical update on the status of these novel therapeutics. 　　INTRODUCTIONnbsp; nbsp; 　　Lung cancer is a major cause of morbidity and mortality worldwide. In the U.S., 172,570 new cases and 163,510 related deaths were predicted for 2005, with lung cancer comprising ~29% of all cancer deaths [1, 2]. Between 80% and 87% of newly diagnosed lung cancers are non-small cell lung cancer (NSCLC). Advanced presentation and lack of effective treatment options afford poor prognoses [3, 4], and despite notable technological progress, improvements in NSCLC survival over the past two decades have been modest [5]. 　　This review focuses on new approaches in NSCLC therapy using monoclonal antibodies (mAbs) and tyrosine kinase inhibitors (TKIs) targeting molecul