Virchows Archiv

, Volume 471, Issue 2, pp 281–293 | Cite as

Molecular genetic and immunotherapeutic targets in metastatic melanoma

  • C. Melis
  • A. Rogiers
  • O. Bechter
  • Joost J. van den Oord
Invited Annual Review Issue


In recent years, melanoma treatment has radically changed with the emergence of targeted therapies and immunotherapies. Both have led to improved survival for patients with advanced or unresectable melanoma. Targeted therapies with BRAF inhibitors in the lead use the presence of activating driver mutations to inhibit tumour growth. Forty to 60% of melanomas harbour BRAF mutations, which makes them susceptible to treatment with BRAF and/or MEK inhibitors. In parallel, the development of immunotherapeutic agents has also expanded. These agents stimulate the endogenous immune system of the patient to eradicate cancer cells. Immune checkpoint inhibitors targeting cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed death 1 (PD-1) resulted in durable responses in a subset of patients. An important issue with immunotherapy lies in the identification of patients who will benefit from treatment. In this review, we will discuss these recent developments in melanoma therapy and highlight the role of the pathologist in both types of treatment.


Melanoma BRAF Targeted therapy Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) Programmed death 1 (PD-1) Immunotherapy 


Compliance with ethical standards

Conflict of interest

C. Melis, J.J. van den Oord and O. Bechter declare that they have no conflict of interest. A. Rogiers received travel support from BMS and Novartis.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • C. Melis
    • 1
  • A. Rogiers
    • 2
  • O. Bechter
    • 2
  • Joost J. van den Oord
    • 1
    • 3
  1. 1.Department of PathologyUniversity Hospitals of Leuven, University of Leuven KULLeuvenBelgium
  2. 2.Department of General Medical OncologyUniversity Hospitals of Leuven, University of Leuven KULLeuvenBelgium
  3. 3.Laboratory Translational Cell and Tissue ResearchUniversity of Leuven, KULLeuvenBelgium

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