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Melanoma pp 667-686 | Cite as

Targeted Therapy in Advanced Melanoma

  • Jeffrey A. Sosman
  • Douglas B. JohnsonEmail author
Reference work entry

Abstract

Molecularly targeted therapy, specifically small molecule therapeutics against particular oncogenes, has transformed the treatment landscape in melanoma and other cancers. Activating mutations in BRAFV600 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.

Keywords

BRAF Targeted therapy NRAS KIT Vemurafenib Dabrafenib Trametinib 

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Northwestern University and Robert H. Lurie Comprehensive Cancer CenterChicagoUSA
  2. 2.Vanderbilt University Medical Center and Vanderbilt Ingram Cancer CenterNashvilleUSA

Section editors and affiliations

  • Keith T. Flaherty
    • 1
  • Boris Bastian
    • 2
  • Hensin Tsao
    • 3
    • 4
  • F. Stephen Hodi
    • 5
    • 6
  1. 1.Henri and Belinda Termeer Center for Targeted TherapiesMGH Cancer CenterBostonUSA
  2. 2.Departments of Dermatology and PathologyUniversity of California, San FranciscoSan FranciscoUSA
  3. 3.AuburndaleUSA
  4. 4.Harvard-MIT Health Sciences and TechnologyCambridgeUSA
  5. 5.FraminghamUSA
  6. 6.Department of Medicine, Brigham and Women's HospitalDana-Farber Cancer InstituteBostonUSA

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