Although advances in cytotoxic treatments have been obtained in several neoplasias, in metastatic melanoma there was no\r\ndrug able to significantly change the natural history of the disease in the last 30 years. In the last decade, translational research\r\nidentified important mechanisms in malignant transformation, invasion, and progression. Signaling pathways can be abnormally\r\nactivated by oncogenes. The identification of oncogenic mutated kinases implicated in this process provides an opportunity for\r\nnew target therapies. The melanoma dependence on BRAF-mutated kinase allowed the development of inhibitors that produced\r\nmajor responses in clinical trials. This is the beginning of a novel class of drugs in metastatic melanoma; the identification of\r\nthe transduction signaling networking and other ââ?¬Å?druggableââ?¬Â kinases is in active research. In this paper, we discuss the ongoing\r\nresearch on cellular signaling inhibition, resistance mechanisms, and strategies to overcome treatment failure.
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