Histone Modifications, Modifiers and Readers in Melanoma Resistance to Targeted and Immune Therapy.
Histone Modifications, Modifiers and Readers in Melanoma Resistance to Targeted and Immune Therapy.
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DOI：
10.3390/cancers7040870
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发表时间：
2015-09-25
期刊：
影响因子：
5.2
通讯作者：
Hersey P
中科院分区：
文献类型：
--
作者：
Gallagher SJ;Tiffen JC;Hersey P
针对MAPK信号传导或免疫系统的新疗法已经彻底改变了黑色素瘤的治疗。不幸的是，这些治疗受到原发性耐药性或获得性耐药性发展的阻碍。在一些黑色素瘤病例中，已经确定了涉及与耐药相关的基因体细胞突变的耐药机制，然而，在其他病例中，耐药的原因在很大程度上仍然无法解释。靶向组蛋白和组蛋白修饰剂的表观遗传因子在驱动黑色素瘤行为中的重要性才刚刚开始被揭示，并为解决治疗抗性问题提供了重要机会。也有越来越多的能力，以靶向这些表观遗传变化的新药，抑制这些修饰，以防止或克服对MAPK抑制剂和免疫疗法的耐药性。本文综述了组蛋白、组蛋白阅读器蛋白和组蛋白定位的变化，这些变化可以介导对新疗法的耐药性，并可以成为未来疗法的靶点。
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.