Current and future trials of targeted therapies in cutaneous melanoma

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19 Scopus citations

Abstract

In order to effectively treat melanoma, targeted inhibition of key mechanistic events regulating melanoma development such as cell proliferation, survival, angiogenesis and invasion or metastasis needs to be accomplished. The Mitogen Activated Protein Kinase (MAPK) pathway has been identified as a key player in melanoma development making this cascade an important therapeutic target. However, identification of the ideal pathway member to therapeutically target for maximal clinical benefit remains a challenge. In normal cells, the MAPK pathway relays extracellular signals from the cell membrane to the nucleus via a cascade of phosphorylation events, which promote cancer development. Dysregulation of the MAPK pathway occurs frequently in many human cancers including melanoma. Mutations in the B-RAF and RAS genes, genetic or epigenetic modifications are the key aberrations observed in this signaling cascade. Constitutive activation of this pathway causes oncogenic transformation of cells by promoting cell proliferation, invasion, metastasis, migration, survival and angiogenesis. This review provides an overview of (a) key members of MAPK signaling regulating melanoma development; (b) key proteins which can serve as biomarkers to assess disease progression; (c) the clinical efficacy of various pharmacological agents targeting MAPK pathway; (d) current clinical trials evaluating downstream targets of the MAPK pathway; (e) issues associated with pharmacological agents such as drug resistance, induction of cancers; and finally (e) various strategies overcoming drug resistance.

Original languageEnglish (US)
Title of host publicationImpact of Genetic Targets on Cancer Therapy
EditorsWafik El-Deiry
Pages223-255
Number of pages33
DOIs
StatePublished - Feb 15 2013

Publication series

NameAdvances in Experimental Medicine and Biology
Volume779
ISSN (Print)0065-2598

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All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Evans, M. S., Madhunapantula, S. R. V., Robertson, G. P., & Drabick, J. J. (2013). Current and future trials of targeted therapies in cutaneous melanoma. In W. El-Deiry (Ed.), Impact of Genetic Targets on Cancer Therapy (pp. 223-255). (Advances in Experimental Medicine and Biology; Vol. 779). https://doi.org/10.1007/978-1-4614-6176-0-10