Current Targeted Agents in Advanced Non-Small Cell Lung Cancer
Luigi Rossi, Marina Minozzi, Anselmo Papa, Maria Colonna, Monica Verrico, Martina Strudel, Enrico Basso, Giovanni Baiano, Giancarlo Arcangeli, Edoardo Francini and Silverio Tomao
AbstractNowadays lung cancer is the main cause of cancer-related death; in a large part of patients cancer is diagnosed in advanced-stage. Among them, Non-Small Cell Lung Cancer (NSCLC) is the most represented subtype of lung cancer. Chemotherapy and radiotherapy represent the standard of care of it. Advanced NSCLC has a standard first-line chemotherapy treatment with platinum based doublets. In the last years the understanding of the molecular pathogenesis of lung cancer is improving more and more, leading to the identification of specific molecular targets in order to select specific therapeutic agents. Bevacizumab is the first recombinant humanized monoclonal antibody binding VEGF to demonstrate clinical benefit in the treatment of non-squamous advanced NSCLC patients. Two types of anti-EGFR targeting agents have reached advanced clinical development: monoclonal antibodies, such as cetuximab, and inhibitors of the EGFR tyrosine kinase enzymatic activity (TKIs). Among TKIs, randomized trials have evaluated the role of gefitinib and erlotinib in first, second, and third line settings and in maintenance, alone or combined with chemotherapy, showing an improvement in survival and responses in selected patients with specific clinical and molecular characteristics. Recently, new molecular targets such as ALK (Anaplastic lymphoma kinase) rearrangement and c-MET overexpression have been identified and new drugs like afatinib, axitinib and crizotinib have been tested in several studies. This review aims to discuss the patents on current and future therapeutic options for advanced NSCLC in the clinical practice.
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