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Dermatology Research and Practice
Volume 2012 (2012), Article ID 259170, 9 pages
Review Article

Targeting the Cellular Signaling: BRAF Inhibition and Beyond for the Treatment of Metastatic Malignant Melanoma

1Department of Dermatology, Institut Gustave Roussy, 114 rue Edouard Vaillant, 948005 Villejuif, France
2Department of Medical Oncology, Institut Jules Bordet, Université Libre de Bruxelles, Boulevard de Waterloo, 121, 1000 Brussels, Belgium

Received 15 July 2011; Accepted 14 September 2011

Academic Editor: Gérald E. Piérard

Copyright © 2012 Felipe Ades and Otto Metzger-Filho. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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