Molecular genetic and immunotherapeutic targets in metastatic melanoma

Molecular genetic and immunotherapeutic targets in metastatic melanoma 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Virchows Archiv Springer Journals

Molecular genetic and immunotherapeutic targets in metastatic melanoma

Molecular genetic and immunotherapeutic targets in metastatic melanoma

Virchows Arch (2017) 471:281–293 DOI 10.1007/s00428-017-2113-3 INVITED ANNUAL REVIEW ISSUE Molecular genetic and immunotherapeutic targets in metastatic melanoma 1 2 2 1,3 C. Melis & A. Rogiers & O. Bechter & Joost J. van den Oord Received: 2 January 2017 /Revised: 14 March 2017 /Accepted: 20 March 2017 /Published online: 29 March 2017 Springer-Verlag Berlin Heidelberg 2017 Abstract In recent years, melanoma treatment has radically Introduction changed with the emergence of targeted therapies and immu- notherapies. Both have led to improved survival for patients Melanoma has an increasing incidence worldwide [1, 2]. In with advanced or unresectable melanoma. Targeted therapies early stages, complete surgical resection is often curative, but with BRAF inhibitors in the lead use the presence of activat- once metastases have occurred, the prognosis looks grim [1, 3]. ing driver mutations to inhibit tumour growth. Forty to 60% of Melanoma is remarkably resistant to various types of chemo- melanomas harbour BRAF mutations, which makes them sus- therapy with few responders and very few durable responses ceptible to treatment with BRAF and/or MEK inhibitors. In [2]. Historically, the median survival for patients with stage IV parallel, the development of immunotherapeutic agents has disease was ≤1year[2]. The limited effectiveness of chemo- also expanded. These agents stimulate the endogenous im- therapy has prompted the search for new therapeutic agents. mune system of the patient to eradicate cancer cells. Immune In recent years, two therapeutic strategies have changed the checkpoint inhibitors targeting cytotoxic T-lymphocyte- landscape of melanoma treatment and have led to improved sur- associated antigen-4 (CTLA-4) and programmed death 1 vival for patients with advanced or unresectable melanoma. First, (PD-1) resulted in durable responses in a subset of patients. the targeted therapies have emerged as the result of the ever- An important issue...
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Publisher
Springer Berlin Heidelberg
Copyright
Copyright © 2017 by Springer-Verlag Berlin Heidelberg
Subject
Medicine & Public Health; Pathology
ISSN
0945-6317
eISSN
1432-2307
D.O.I.
10.1007/s00428-017-2113-3
Publisher site
See Article on Publisher Site

Abstract

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.

Journal

Virchows ArchivSpringer Journals

Published: Mar 29, 2017

References

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