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Published on: April 5, 2018
Histone Modifications, Modifiers and Readers in Melanoma Resistance to Targeted and Immune Therapy
Stuart J Gallagher1,2, Jessamy C Tiffen3,4, Peter Hersey5,6
1Melanoma Immunology and Oncology Group, Centenary Institute, University of Sydney, Camperdown 2050, Australia. s.gallagher@centenary.org.au.
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.
Insights
New epigenetic strategies targeting histone modifications offer promising avenues to overcome melanoma therapy resistance. Understanding these epigenetic factors is key to developing more effective treatments for melanoma patients.
Area of Science:
- Oncology
- Epigenetics
- Melanoma Research
Background:
- Melanoma treatments targeting MAPK signaling and the immune system have revolutionized care.
- Therapy resistance, both primary and acquired, remains a significant challenge in melanoma treatment.
- While genetic mutations explain some resistance, many mechanisms remain unclear.
Purpose of the Study:
- To review the role of epigenetic factors, specifically histones and histone modifiers, in melanoma therapy resistance.
- To highlight the potential of targeting epigenetic modifications to overcome resistance to current melanoma therapies.
- To focus on histone changes, reader proteins, and positioning as mediators of resistance.
Main Methods:
- Literature review of epigenetic mechanisms in melanoma resistance.
- Analysis of studies investigating histone modifications and their impact on therapy.
- Examination of emerging therapeutic strategies targeting epigenetic alterations.
Main Results:
- Epigenetic factors, including histone modifications and positioning, play a crucial role in melanoma's response to therapy.
- These epigenetic changes can mediate resistance to both MAPK inhibitors and immunotherapy.
- Targeting epigenetic modifications presents a viable strategy to combat therapy resistance.
Conclusions:
- Epigenetic alterations are critical drivers of melanoma therapy resistance.
- Targeting histones, histone modifiers, and related pathways offers a promising approach to overcome treatment failure.
- Further research into epigenetic mechanisms is essential for developing next-generation melanoma therapies.
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