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Melanoma pp 1–20Cite as

Targeted Therapy in Advanced Melanoma

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Abstract

Molecularly targeted therapy, specifically small molecule therapeutics against particular oncogenes, has transformed the treatment landscape in melanoma and other cancers. Activating mutations in BRAF V600 produce constitutive activation of the mitogen-activated protein kinase (MAPK) pathway, causing unrestrained growth in nearly half of all melanomas. In turn, therapeutic blockade of this pathway through BRAF inhibitors produces dramatic clinical responses and improved survival compared to traditional cytotoxic chemotherapy. The addition of downstream MAPK blockade via MEK inhibition has further improved clinical outcomes. Although initial responses are impressive in most patients, and durable responses occasionally occur, acquired resistance remains a major barrier to long-term efficacy with these agents. A number of other potential therapeutic targets have been identified among other subsets of melanoma, including those with NRAS mutations, KIT mutations, and atypical BRAF alterations. Further, combinatorial regimens targeted MAPK and other pathways (including CDK4/6 and PI3K/AKT pathways) have shown early promise. This chapter reviews the development, current clinical activity, and future development directions for targeted therapy in melanoma.

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Authors and Affiliations

  1. Northwestern University and Robert H. Lurie Comprehensive Cancer Center, Chicago, IL, USA

    Jeffrey A. Sosman

  2. Vanderbilt University Medical Center and Vanderbilt Ingram Cancer Center, Nashville, TN, USA

    Douglas B. Johnson

Authors
  1. Jeffrey A. Sosman
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  2. Douglas B. Johnson
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Correspondence to Douglas B. Johnson .

Editor information

Editors and Affiliations

  1. Harvard/MGH Cutaneous Biology Research C Massachusetts General Hospital, Boston, Massachusetts, USA

    David E. Fisher

  2. Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York, USA

    Boris C. Bastian

Section Editor information

  1. Henri and Belinda Termeer Center for Targeted Therapies, MGH Cancer Center, Boston, MA, USA

    Keith T. Flaherty

  2. Departments of Dermatology and Pathology, University of California, San Francisco, San Francisco, CA, USA

    Boris Bastian

  3. Auburndale, MA, USA

    Hensin Tsao

  4. Harvard-MIT Health Sciences and Technology, Cambridge, MA, USA

    Hensin Tsao

  5. Framingham, MA, USA

    F. Stephen Hodi

  6. Department of Medicine, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Boston, MA, USA

    F. Stephen Hodi

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Sosman, J.A., Johnson, D.B. (2018). Targeted Therapy in Advanced Melanoma. In: Fisher, D., Bastian, B. (eds) Melanoma. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-7322-0_12-1

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