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Molekulargenetische Diagnostik – zielgerichtete Therapie des malignen Melanoms

Molecular genetic diagnostics—targeted therapy for malignant melanoma

  • Leitthema
  • Published:
Der Onkologe Aims and scope

Zusammenfassung

Hintergrund

Mit der Identifizierung der Schlüsselrolle des MAPK-Signalwegs (MAPK „mitogen-activated protein kinase“) für die Entstehung und Progression des malignen Melanoms gelang ein Durchbruch in dessen Behandlung. Die Entwicklung zielgerichteter Therapien und Immuntherapien führte zu einem breiten therapeutischen Spektrum in der Behandlung fortgeschrittener oder metastasierter Melanome.

Ziel

Dieser Artikel befasst sich mit der Wirksamkeit der aktuellen selektiven Kinaseinhibitoren bei der Behandlung des malignen Melanoms mit nachgewiesener BRAF-Mutation und auch den seltener vorkommenden Mutationen im NRAS- und cKIT-Gen. Die Ergebnisse neuester klinischer Studien einschließlich des Toxizitätsprofils sowie neue Therapieansätze werden beschrieben.

Material und Methoden

Diese Arbeit basiert auf einer selektiven Literaturrecherche in der Datenbank PubMed und ClinicalTrials zum Thema Behandlung des fortgeschrittenen Melanoms.

Ergebnisse

Eine Kombination von BRAF- und MEK-Inhibitoren führt zu einer Steigerung des Therapieansprechens und des Gesamtüberlebens im Vergleich zur Chemotherapie oder Monotherapie. Weitere spezifische Inhibitoren zeigen vielversprechende Resultate.

Diskussion

Durch die zielgerichtete Therapie und Checkpointblockade hat sich die Prognose des fortgeschrittenen und metastasierten Melanoms deutlich verbessert. Eine Kombination dieser therapeutischen Ansätze, könnte zukünftig in der Behandlung des Melanoms eine wichtige Rolle spielen. Sowohl eine detaillierte genetische Analyse des Tumors als auch ein besseres Verständnis der biologischen Prozesse sind notwendig, um insbesondere hinsichtlich der Resistenzmechanismen die Wirksamkeit moderner Melanomtherapien zu verbessern.

Abstract

Background

The identification of the MAPK signaling pathway as a key factor in the origin and progress of malignant melanoma led to a breakthrough in its treatment. The development of targeted therapies as well as immunotherapies added a broad therapeutic scope in the treatment of advanced or metastatic melanomas.

Aim

This article deals with the efficacy of current selective kinase inhibitors in the treatment of malignant melanoma with BRAF mutations and other rare mutations, such as NRAS and cKIT. Results of the latest clinical studies with their toxicity profiles and new therapeutic approaches are described.

Material and methods

This article is based on a selective literature search in the PubMed and Clinicaltrials database for the treatment of advanced melanoma.

Results

A combination of BRAF and MEK inhibitors leads to an improved response rate and increase in overall survival compared to chemotherapy or monotherapy. Other specific inhibitors show promising results as well.

Discussion

Targeted therapies and checkpoint inhibitors significantly improve the prognosis of advanced and metastatic melanoma. In the future a combination of these therapeutic approaches could play an important role in the treatment of melanoma. A detailed genetic analysis of the tumor as well as a profound understanding of biological processes are necessary to improve the efficacy of modern treatment of melanoma, particularly regarding resistance and molecular escape mechanisms.

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Authors and Affiliations

  1. Zentrum für Dermato-Onkologie, Südwestdeutsches Tumorzentrum, Universitäts-Hautklinik, Eberhard-Karls-Universität Tübingen, Liebermeisterstr. 25, 72076, Tübingen, Deutschland

    Katharina Pietschke, Diana Lomberg, Thomas Kurt Eigentler &  Ulrike Leiter

Authors
  1. Katharina Pietschke
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  2. Diana Lomberg
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  3. Thomas Kurt Eigentler
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  4. Ulrike Leiter
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Corresponding author

Correspondence to Ulrike Leiter.

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Interessenkonflikt

K. Pietschke, D. Lomberg, T.K. Eigentler und U. Leiter geben an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

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Pietschke, K., Lomberg, D., Eigentler, T.K. et al. Molekulargenetische Diagnostik – zielgerichtete Therapie des malignen Melanoms. Onkologe 24, 472–477 (2018). https://doi.org/10.1007/s00761-018-0373-4

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  • DOI: https://doi.org/10.1007/s00761-018-0373-4

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