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Review
. 2011 Feb 1;104(3):392-8.
doi: 10.1038/sj.bjc.6606030. Epub 2010 Dec 7.

Targeting BRAF for patients with melanoma

H-T Arkenau  1 , R Kefford, G V Long
Affiliations
Review

Targeting BRAF for patients with melanoma

H-T Arkenau et al. Br J Cancer. .

Abstract

The prognosis of patients with metastatic melanoma is poor and not influenced by systemic therapy with cytotoxic drugs. New targeted agents directed against the RAS-RAF-MEK-ERK pathway show promising activity in early clinical development and particular interest is focused on selective inhibitors of mutant BRAF, which is present in one half of the cases of metastatic melanoma. The majority of patients on early trials of these drugs develop secondary resistance and subsequent disease progression and it is, therefore, critical to understand the underlying escape mechanisms leading to resistance.

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Figures

Figure 1
Figure 1
The MAPK pathway activation in melanoma. Oncogenic NRAS, BRAF, GNAQ and CKIT signal through the MAPK pathway. Oncogenic NRAS also induces the phosphatidylinositol-3′ kinase (PI3K) cascade. MAPK signalling can lead to proliferation in transformed cells, but also induces a potent form of growth arrest, known as senescence in normal melanocytes. The approximate proportion of melanomas with mutations are shown. GPCR=G-protein coupled receptor.
Figure 2
Figure 2
Common types of BRAF mutations in melanoma (Wan et al, 2004).
See this image and copyright information in PMC

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