Cancer letters
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The prognosis in advanced non-small cell cancer (NSCLC) remains poor despite the introduction of several new cytotoxic drugs in the past decade. New approaches are required, and an improved understanding of lung cancer biology is identifying molecular mechanisms that are potential targets for novel therapies. ⋯ This reflects the molecular heterogeneity of the disease; further clinical progress will require improved patient selection for treatment with both novel agents and established chemotherapy drugs. Here, we review recent advances in NSCLC biology likely to provide insight into such selection strategies.
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Despite the remarkable results achieved with imatinib for the treatment of chronic myeloid leukaemia, the emergence of resistance to this tyrosine kinase inhibitor has become a significant problem. Much progress has been recently made in elucidating the mechanisms which underlie imatinib resistance. The most common cause of such drug resistance is the selection of leukaemic clones with point mutations in the Abl kinase domain leading to amino acid substitutions which prevent the appropriate binding of the drug. ⋯ There is a pressing need, therefore, to develop and test novel drugs and strategies. Two such compounds are now being explored in clinical trials. This review will describe the molecular basis of imatinib-resistance and strategies to overcome resistance.