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Histone Modifications, Modifiers and Readers in Melanoma Resistance to Targeted and Immune Therapy

The treatment of melanoma has been revolutionized by new therapies targeting MAPK signaling or the immune system. Unfortunately these therapies are hindered by either primary resistance or the development of acquired resistance. Resistance mechanisms involving somatic mutations in genes associated w...

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Detalles Bibliográficos
Autores principales: Gallagher, Stuart J, Tiffen, Jessamy C, Hersey, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4695870/
https://www.ncbi.nlm.nih.gov/pubmed/26426052
http://dx.doi.org/10.3390/cancers7040870
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author Gallagher, Stuart J
Tiffen, Jessamy C
Hersey, Peter
author_facet Gallagher, Stuart J
Tiffen, Jessamy C
Hersey, Peter
author_sort Gallagher, Stuart J
collection PubMed
description The treatment of melanoma has been revolutionized by new therapies targeting MAPK signaling or the immune system. Unfortunately these therapies are hindered by either primary resistance or the development of acquired resistance. Resistance mechanisms involving somatic mutations in genes associated with resistance have been identified in some cases of melanoma, however, the cause of resistance remains largely unexplained in other cases. The importance of epigenetic factors targeting histones and histone modifiers in driving the behavior of melanoma is only starting to be unraveled and provides significant opportunity to combat the problems of therapy resistance. There is also an increasing ability to target these epigenetic changes with new drugs that inhibit these modifications to either prevent or overcome resistance to both MAPK inhibitors and immunotherapy. This review focuses on changes in histones, histone reader proteins and histone positioning, which can mediate resistance to new therapeutics and that can be targeted for future therapies.
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spelling pubmed-46958702016-01-19 Histone Modifications, Modifiers and Readers in Melanoma Resistance to Targeted and Immune Therapy Gallagher, Stuart J Tiffen, Jessamy C Hersey, Peter Cancers (Basel) Review The treatment of melanoma has been revolutionized by new therapies targeting MAPK signaling or the immune system. Unfortunately these therapies are hindered by either primary resistance or the development of acquired resistance. Resistance mechanisms involving somatic mutations in genes associated with resistance have been identified in some cases of melanoma, however, the cause of resistance remains largely unexplained in other cases. The importance of epigenetic factors targeting histones and histone modifiers in driving the behavior of melanoma is only starting to be unraveled and provides significant opportunity to combat the problems of therapy resistance. There is also an increasing ability to target these epigenetic changes with new drugs that inhibit these modifications to either prevent or overcome resistance to both MAPK inhibitors and immunotherapy. This review focuses on changes in histones, histone reader proteins and histone positioning, which can mediate resistance to new therapeutics and that can be targeted for future therapies. MDPI 2015-09-25 /pmc/articles/PMC4695870/ /pubmed/26426052 http://dx.doi.org/10.3390/cancers7040870 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Gallagher, Stuart J
Tiffen, Jessamy C
Hersey, Peter
Histone Modifications, Modifiers and Readers in Melanoma Resistance to Targeted and Immune Therapy
title Histone Modifications, Modifiers and Readers in Melanoma Resistance to Targeted and Immune Therapy
title_full Histone Modifications, Modifiers and Readers in Melanoma Resistance to Targeted and Immune Therapy
title_fullStr Histone Modifications, Modifiers and Readers in Melanoma Resistance to Targeted and Immune Therapy
title_full_unstemmed Histone Modifications, Modifiers and Readers in Melanoma Resistance to Targeted and Immune Therapy
title_short Histone Modifications, Modifiers and Readers in Melanoma Resistance to Targeted and Immune Therapy
title_sort histone modifications, modifiers and readers in melanoma resistance to targeted and immune therapy
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4695870/
https://www.ncbi.nlm.nih.gov/pubmed/26426052
http://dx.doi.org/10.3390/cancers7040870
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