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NRAS mutant melanoma: biological behavior and future strategies for therapeutic management

Oncogene volume 32, pages 3009–3018 (2013)Cite this article

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Abstract

The recent years have seen a significant shift in the expectations for the therapeutic management of disseminated melanoma. The clinical success of BRAF targeted therapy suggests that long-term disease control may one day be a reality for genetically defined subgroups of melanoma patients. Despite this progress, few advances have been made in developing targeted therapeutic strategies for the 50% of patients whose melanomas are BRAF wild-type. The most well-characterized subgroup of BRAF wild-type tumors is the 15–20% of all melanomas that harbor activating NRAS (Neuroblastoma Rat Sarcoma Virus) mutations. Emerging preclinical and clinical evidence suggests that NRAS mutant melanomas have patterns of signal transduction and biological behavior that is distinct from BRAF mutant melanomas. This overview will discuss the unique clinical and prognostic behavior of NRAS mutant melanoma and will summarize the emerging data on how NRAS-driven signaling networks can be translated into novel therapeutic strategies.

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Acknowledgements

Work in the Smalley lab is supported by Grants U54 CA143970-01 and R01 CA161107-01 from the National Institutes of Health, The Harry Lloyd Trust and the State of Florida (09BN-14).

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Authors and Affiliations

  1. Department of Molecular Oncology, Tampa, FL, USA

    I V Fedorenko & K S M Smalley

  2. The Comprehensive Melanoma Research Center, The Moffitt Cancer Center, Tampa, FL, USA

    I V Fedorenko, G T Gibney & K S M Smalley

  3. Department of Cutaneous Oncology, Tampa, FL, USA

    G T Gibney & K S M Smalley

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  1. I V Fedorenko
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  2. G T Gibney
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  3. K S M Smalley
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Correspondence to K S M Smalley.

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Fedorenko, I., Gibney, G. & Smalley, K. NRAS mutant melanoma: biological behavior and future strategies for therapeutic management. Oncogene 32, 3009–3018 (2013). https://doi.org/10.1038/onc.2012.453

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  • DOI: https://doi.org/10.1038/onc.2012.453

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