Lancet
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Non-small-cell lung cancer is often diagnosed at the metastatic stage, with median survival of just 1 year. The identification of driver mutations in the epidermal growth factor receptor (EGFR) as the primary oncogenic event in a subset of lung adenocarcinomas led to a model of targeted treatment and genetic profiling of the disease. EGFR tyrosine kinase inhibitors confer remission in 60% of patients, but responses are short-lived. ⋯ Overexpression of AXL and reduced MED12 function are hallmarks of resistance to tyrosine kinase inhibitors in EGFR-mutant non-small-cell lung cancer. Crosstalk between signalling pathways is another mechanism of resistance; therefore, identification of the molecular components involved could lead to the development of combination therapies cotargeting these molecules instead of EGFR tyrosine kinase inhibitor monotherapy. Additionally, novel biomarkers could be identified through deep sequencing analysis of serial rebiopsies before and during treatment.
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Deaths from lung cancer exceed those from any other type of malignancy, with 1·5 million deaths in 2010. Prevention and smoking cessation are still the main methods to reduce the death toll. The US National Lung Screening Trial, which compared CT screening with chest radiograph, yielded a mortality advantage of 20% to participants in the CT group. ⋯ When questions about effectiveness and cost-effectiveness have been answered, which will await publication of the largest European trial, NELSON, and pooled analysis of European CT screening trials, we discuss the main topics that will need consideration. These unresolved issues are risk prediction models to identify patients for CT screening; radiological protocols that use volumetric analysis for indeterminate nodules; options for surgical resection of CT-identified nodules; screening interval; and duration of screening. We suggest that a demonstration project of biennial screening over a 4-year period should be undertaken.