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Cutaneous Melanoma pp 1–19Cite as

Targeted Therapies for BRAF-Mutant Metastatic Melanoma

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Abstract

Melanoma is characterized by frequent mutations in the serine-threonine kinase encoding gene BRAF, triggering unrestrained MAPK signaling. In the 40–50% of patients harboring these mutations, inhibiting mutant BRAF or its downstream signaling partner MEK leads to dramatic clinical benefits in patients. Although either BRAF or MEK inhibitors improve outcomes compared with cytotoxic chemotherapy, acquired resistance occurs within 9–12 months in almost all patients and is largely due to MAPK signaling reactivation. Combined BRAF and MEK inhibition forestalls this resistance and has led to improved survival in patients with metastatic BRAF-mutant melanoma with a median progression-free survival of approximately 1 year. Acquired resistance remains a major barrier to long-term success although up to 20% of patients have durable responses (lasting >5 years) with these agents. Combining these MAPK pathway inhibitors with immunotherapies and achieving more thorough pathway blockade (e.g., with ERK inhibitors) are ongoing areas of research.

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Authors and Affiliations

  1. Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA

    Douglas B. Johnson

  2. Department of Medicine, Vanderbilt Ingram Cancer Center, Nashville, TN, USA

    Douglas B. Johnson

  3. Department of Dermatology, University Hospital Zurich, Zurich, Switzerland

    Reinhard Dummer

  4. Department of Dermatology, University of Zurich, Zurich, Switzerland

    Reinhard Dummer

  5. Department of Medicine, Massachusetts General Hospital, Boston, MA, USA

    Keith T. Flaherty

  6. Tumor Biology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA

    Keiran S. Smalley

Authors
  1. Douglas B. Johnson
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  2. Reinhard Dummer
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  3. Keith T. Flaherty
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  4. Keiran S. Smalley
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Corresponding author

Correspondence to Douglas B. Johnson .

Editor information

Editors and Affiliations

  1. Division of Surgical Oncology, University of Texas Southwestern, Dallas, TX, USA

    Charles Balch

  2. Division of Surgery, UT MD Anderson Cancer Center, Houston, TX, USA

    Jeffrey Gershenwald

  3. Melanoma Institute of Australia, Wollstonecraft, Australia

    John Thompson

  4. Georgetown Medical Center, Washington, DC, USA

    Michael Atkins

  5. Melanoma and Skin Cancer Program, University of Pittsburgh, Pittsburgh, PA, USA

    John Kirkwood

  6. University of Sydney, Sydney, NSW, Australia

    Richard Kefford

  7. Department of Dermatology, Harvard Medical Center, Boston, MA, USA

    Arthur Sober

  8. Department of Dermatology, Memorial Sloan Kettering, New York, NY, USA

    Allan Halpern

  9. Department of Dermatology, University Hospital, Tübingen, Tübingen, Germany

    Claus Garbe

  10. Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown NSW, Australia

    Richard Scolyer

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Johnson, D.B., Dummer, R., Flaherty, K.T., Smalley, K.S. (2019). Targeted Therapies for BRAF-Mutant Metastatic Melanoma. In: Balch, C., et al. Cutaneous Melanoma. Springer, Cham. https://doi.org/10.1007/978-3-319-46029-1_40-1

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  • DOI: https://doi.org/10.1007/978-3-319-46029-1_40-1

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-46029-1

  • Online ISBN: 978-3-319-46029-1

  • eBook Packages: Springer Reference MedicineReference Module Medicine

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