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Current and Future Trials of Targeted Therapies in Cutaneous Melanoma

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Impact of Genetic Targets on Cancer Therapy

Part of the book series: Advances in Experimental Medicine and Biology ((volume 779))

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.

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Grant Support

NIH CA-127892-01A and The Foreman Foundation for Melanoma Research (GPR).

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Authors and Affiliations

  1. Penn State Cancer Institute, Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA

    Matthew S. Evans & Joseph J. Drabick

  2. Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA

    SubbaRao V. Madhunapantula & Gavin P. Robertson

  3. Department of Pathology, Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA

    Gavin P. Robertson

  4. Department of Dermatology, Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA

    Gavin P. Robertson

  5. Department of Surgery, Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA

    Gavin P. Robertson

  6. Penn State Melanoma Center, Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA

    Gavin P. Robertson & Joseph J. Drabick

  7. Penn State Melanoma Therapeutics Program, Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA

    Gavin P. Robertson

  8. The Foreman Foundation for Melanoma Research, Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA

    Gavin P. Robertson

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  1. Matthew S. Evans
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    Wafik S El-Deiry

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Evans, M.S., Madhunapantula, S.V., Robertson, G.P., Drabick, J.J. (2013). Current and Future Trials of Targeted Therapies in Cutaneous Melanoma. In: El-Deiry, W. (eds) Impact of Genetic Targets on Cancer Therapy. Advances in Experimental Medicine and Biology, vol 779. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6176-0_10

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