Tyrosine Kinases as Molecular Targets to Inhibit Cancer Progression and Metastasis

During the last decades, the improvement of our knowledge of the mechanisms responsible for cancer development has led to the introduction of new promising strategies of treatment, based on "molecular targeted" drugs. These drugs are designed to act on specific molecules, identified as major players in the maintenance of the malignant status. The development of inhibitors, mainly monoclonal antibodies and small-molecules, directed against activated oncogenes has been the most widely used approach for this kind of treatment. Among the oncogenes implicated in human cancers, tyrosine kinases play a critical role. This observation, together with the discovery that cancer cells can be dependent for their survival from the continuous expression of activated oncogenes (a concept defined as "oncogene addiction"), has made protein kinases ideal targets for targeted therapy in cancer. As the field of targeted therapies is now rapidly growing and a comprehensive survey would be too wide, this review will thus mainly focus on strategies aimed at inhibiting tyrosine kinases and their signal transduction pathways.