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Cancers 2015, 7(4), 1959-1982; doi:10.3390/cancers7040870

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

1
Melanoma Immunology and Oncology Group, Centenary Institute, University of Sydney, Camperdown 2050, Australia
2
Melanoma Institute Australia, Crow's Nest 2065, Sydney, Australia
*
Author to whom correspondence should be addressed.
Academic Editor: Chyi-Chia Richard Lee
Received: 31 July 2015 / Revised: 17 September 2015 / Accepted: 18 September 2015 / Published: 25 September 2015
(This article belongs to the Special Issue Current Topics in Cutaneous Melanoma)
View Full-Text   |   Download PDF [710 KB, uploaded 25 September 2015]   |  

Abstract

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. View Full-Text
Keywords: BRAF; RAF; MEK; immunotherapy; HDAC; histones; methyltransferase; bromodomain; BET; chromatin modifiers; resistance; PRC2; EZH2; PD-L1; PD-1 BRAF; RAF; MEK; immunotherapy; HDAC; histones; methyltransferase; bromodomain; BET; chromatin modifiers; resistance; PRC2; EZH2; PD-L1; PD-1
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Gallagher, S.J.; Tiffen, J.C.; Hersey, P. Histone Modifications, Modifiers and Readers in Melanoma Resistance to Targeted and Immune Therapy. Cancers 2015, 7, 1959-1982.

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