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Novel Approaches in Melanoma Prevention and Therapy

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Advances in Nutrition and Cancer

Part of the book series: Cancer Treatment and Research ((CTAR,volume 159))

Abstract

The incidence of cutaneous melanoma has risen at a rate significantly higher than that for other malignancies. This increase persists despite efforts to educate the public about the dangers of excess exposure to UV radiation from both the sun and tanning beds. Melanoma affects a relatively younger population and is notorious for its propensity to metastasize and for its poor response to current therapeutic regimens. These factors make prevention an integral component to the goal of decreasing melanoma-related mortality. Transformation of melanocytes into malignant melanoma involves the interplay between genetic factors, UV exposure, and the tumor microenvironment. The roles of UV radiation in the etiology of melanoma are mediated by both direct damage of DNA through formation of photoproducts and production of reactive oxygen species (ROS). Many of the promising antioxidant agents under development for the prevention of melanoma are derived from foodstuffs. B-Raf is a member of the Raf kinase family of serine/threonine-specific protein kinases that plays a role in regulating the MAP kinase/ERKs signaling pathway. About 50 % of melanomas harbor activating BRAF mutations. BRAF mutations are found in 59 % of the melanomas arising in skin with intermittent sun exposure, such as trunk and arms, as compared with only 23 % of the acral melanomas, 11 % of mucosal melanomas, and 0 % of uveal melanomas. Two new agents, ipilimumab and vemurafenib, have been shown to improve outcome of advanced melanoma as presented at the plenary session of the 2011 annual meeting of the American Society of Clinical Oncology. Vemurafenib is the first personalized compound which demonstrated an improvement in progression-free survival (PFS) and overall survival (OS) in metastatic melanoma harboring the BRAFV600 mutation and represents the first drug of a class that exerts its anti-proliferative activity through inhibition of a highly specific molecular target. GSK2118436 (dabrafenib), the second BRAF inhibitor, in phase I and II trial obtained similar results to vemurafenib. A phase III trial is now ongoing. Taken together, the early clinical development of vemurafenib and dabrafenib clearly confirms that BRAF inhibitors can halt or reverse disease in patients with melanomas carrying this mutation, improving survival times compared with historically standard treatments (chemotherapy and interleukin-2). The clinical development of other new BRAF inhibitors such as RAF265 and LGX818 is now ongoing. Combination strategies of BRAF inhibitors with ipilimumab, an anti-CTLA-4 antibody, and/or MEK inhibitors or metformin are now under investigation in clinical trials.

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Abbreviations

GTE:

Green tea extracts

EGCG:

epigallocatechin-3-gallate

CSD:

chronic sun damage

CTLA-4:

cytotoxic T lymphocyte–associated antigen 4

cSCC:

Cutaneous squamous cell carcinoma

VEGFR-2:

vascular endothelial growth factor receptor 2

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Author information

Authors and Affiliations

  1. Unit of Melanoma, Immunotherapy and Innovative Therapies, Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione G. Pascale, Via Mariano Semmola, 80131, Naples, Italy

    Antonio M. Grimaldi & Paolo A. Ascierto

  2. Huntsman Cancer Institute, University of Utah, Melanoma and Cutaneous Oncology Program, Salt Lake, UT, USA

    Pamela B. Cassidy & Sancy Leachmann

Authors
  1. Antonio M. Grimaldi
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  2. Pamela B. Cassidy
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  3. Sancy Leachmann
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  4. Paolo A. Ascierto
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Corresponding author

Correspondence to Paolo A. Ascierto .

Editor information

Editors and Affiliations

  1. Dept. of Biochemistry and Biophysics, Second University of Naples, Naples, Italy

    Vincenzo Zappia

  2. Clinical and Experimental Medicine, University of Naples "Federico II", Naples, Italy

    Salvatore Panico

  3. Institute of Food Sciences National Research Council, Avellino, Italy

    Gian Luigi Russo

  4. Dept. of Experimental Oncology, National Cancer Institute, Naples, Italy

    Alfredo Budillon

  5. Dept. of Biochemistry and Biophysics, Second University of Naples, Naples, Italy

    Fulvio Della Ragione

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© 2014 Springer-Verlag Berlin Heidelberg

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Grimaldi, A.M., Cassidy, P.B., Leachmann, S., Ascierto, P.A. (2014). Novel Approaches in Melanoma Prevention and Therapy. In: Zappia, V., Panico, S., Russo, G., Budillon, A., Della Ragione, F. (eds) Advances in Nutrition and Cancer. Cancer Treatment and Research, vol 159. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-38007-5_25

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  • DOI: https://doi.org/10.1007/978-3-642-38007-5_25

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