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J Invest Dermatol. 2010 Jan;130(1):28-37. doi: 10.1038/jid.2009.177.

Understanding melanoma signaling networks as the basis for molecular targeted therapy.

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  • The Molecular Oncology Program and Comprehensive Melanoma Research Center, The Moffitt Cancer Center, Tampa, Florida, USA. Keiran.Smalley@moffitt.org


Despite years of research, there has been little improvement in survival for patients with disseminated melanoma. Recent work has identified mutations in BRAF and NRAS, leading to constitutive mitogen-activated protein kinase (MAPK) pathway as well as constitutive activity in the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway, as being critical events in melanoma growth and progression. In the current review, we discuss how these complex mutational and signaling profiles can be understood using a network biology approach, and suggest how an understanding of the key signaling nodes involved in progression and survival will lead to improvements in melanoma therapy.

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