الفهرس 
Management of advanced NSCLCOnly 14 pages are availabe for public view
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Abstract
Worldwide, lung cancer occurred in approximately 1.8 million patients in 2012 and caused an estimated 1.6 million deaths. Tobacco smoking is a major modifiable risk factor in the development of lung cancer and accounts for 85% of all lung cancer–related deaths.
Approximately 5% to 10 % of lung cancer patients are asymptomatic at presentation. Most lung cancer patients who are symptomatic have advanced disease. The diagnosis of lung cancer can be made on tissue specimens such as endobronchial and transbronchial core biopsies or resected specimens, or by assessment of cytological specimens such as transbronchial or transthoracic fine-needle aspirates, bronchial brushing and washings, broncho-alveolar lavage or sputum or pleural fluid.
The WHO divides lung cancer into 2 major classes based on its biology, therapy, and prognosis: NSCLC and small cell lung cancer [SCLC]. NSCLC accounts for more than 85% of all lung cancer cases. A new multidisciplinary classification of lung adenocarcinoma has been proposed jointly by the International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS), and European Respiratory Society (ERS).
Molecular profiling, the prospective analysis of tumor genetic expression, proteomic profile, deregulated cellular pathways and/or somatic mutations could identify patients who are most likely to benefit from a specific targeted drug and thereby, potentially improve outcomes, minimize toxic effects and abbreviate drug development. However, the increasing number of driver mutations in ever smaller subsets of patients and the availability of an array of candidate drugs ,have made clinical application of this paradigm challenging.
Epidermal growth factor receptor (EGFR) is normally found on the surface of epithelial cells and is often overexpressed in a variety of human malignancies. Presence of EGFR-activating mutations represents a critical biological determinant for proper therapy selection in patients with lung cancer. KRAS (also known as V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) gene mutations are associated with intrinsic TKI resistance, and KRAS gene sequencing could be useful for the selection of patients as candidates for TKI therapy.
EML4-ALK, gene rearrangements in a subset of anaplastic large cell lymphomas (ALCL), have been recognized for over 15 years. The fusion between echinoderm microtubule--associated protein-like 4 (EML4) and ALK has recently been identified in a subset of patients with NSCLC. EML4-ALK NSCLC represents a unique subset of NSCLC patients for whom ALK inhibitors may represent a very effective therapeutic stratege.
Treatment differs according to the histological subtype of the disease , the stage , patient’s age, gender and performance status and all this agents can predict survival too. Although systemic chemotherapy is the standard treatment for patients with advanced stage NSCLC, its results may have reached a plateu and will be difficult to obtain better results by chemotherapy alone. So new biological agents have been added to improve outcome.
Specific targeted therapies have been developed for the treatment of advanced lung cancer like bevacizumab which is a recombinant monoclonal antibody that blocks the vascular endothelial growth factor (VEGF), erlotinib gefitinib and afatinib which are small molecule inhibitors of EGFR, crizotinib and ceritinib which are small molecule inhibitor that targets ALK.
All of these targeted agents got FDA approval for usage for treatment of non small cell lung cancer in different lines of treatment based on trails proves their safety and efficacy in changing tumour response either alone or combined with chemotherapy. With more than 500 other targeted agents under development, the prospects of identifying novel therapies that can benefit individal patients with lung cancer are bright.