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Molecularly targeted therapy for metastatic melanoma

Jeffrey A Sosman, MD
Section Editor
Michael B Atkins, MD
Deputy Editor
Michael E Ross, MD


Although the incidence of malignant melanoma is increasing, most cases are diagnosed at an early stage. In that setting, surgical excision is curative in most cases, and patients at high risk of developing metastatic disease may benefit from adjuvant immunotherapy with interferon alfa or ipilimumab (algorithm 1) [1]. (See "Initial surgical management of melanoma of the skin and unusual sites" and "Adjuvant therapy for cutaneous melanoma".)

The management of patients with disseminated disease is a difficult problem (algorithm 2). Approaches that have been shown to provide clinically important benefit for appropriately selected patients with disseminated melanoma include immunotherapy with high-dose interleukin-2 (IL-2), immunotherapy with antibodies targeting programmed cell death protein 1 (PD-1) and/or with ipilimumab (a monoclonal antibody targeting cytotoxic T-lymphocyte-associated protein 4 [CTLA-4]), and inhibition of the mitogen-activated protein (MAP) kinase pathway in patients whose tumors contain a V600 mutation in the BRAF gene using either a BRAF inhibitor or an MEK inhibitor. There are no randomized trials that compare targeted therapy with immunotherapy, and there are no prospective data on the appropriate sequencing of these therapies for patients with a BRAFV600 mutation.

The use of targeted therapies in the treatment of advanced melanoma will be reviewed here.


An understanding of the role of activation of the mitogen-activated protein (MAP) kinase pathway has led to the identification of several drug targets (figure 1). This is resulting in the development of important therapeutic approaches for the treatment of advanced melanoma in various patient subsets. These include inhibition of BRAF, MEK, NRAS, and KIT.

The general approach to the treatment of advanced melanoma and the integration of targeted therapy with other treatment modalities is presented separately (algorithm 2). (See "Overview of the management of advanced cutaneous melanoma" and "The molecular biology of melanoma".)

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Literature review current through: Nov 2017. | This topic last updated: Oct 17, 2017.
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