Roesch Alexander, Paschen Annette, Landsberg Jenny, Helfrich Iris, Becker Jürgen C, Schadendorf Dirk
Department of Dermatology, Venereology, and Allergology, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany; German Cancer Consortium (DKTK), Partner Site Essen/Düsseldorf, West German Cancer Center, University of Duisburg-Essen, 45122 Essen, Germany.
Department of Dermatology, Venereology, and Allergology, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany; German Cancer Consortium (DKTK), Partner Site Essen/Düsseldorf, West German Cancer Center, University of Duisburg-Essen, 45122 Essen, Germany.
Eur J Cancer. 2016 May;59:109-112. doi: 10.1016/j.ejca.2016.02.023. Epub 2016 Mar 26.
Despite the recent success of MAPK and immune checkpoint inhibitors in advanced melanoma, intrinsic and acquired resistance mechanisms determine the efficacy of these therapeutic approaches. Therapy resistance in melanoma is not solely driven by genetic evolution, but also by epigenetically driven adaptive plasticity. Melanoma cells are shifting between different transcriptional programs, cell cycle states and differentiation phenotypes reflecting a highly dynamic potential to adapt to various exogenous stressors including immune attack or cancer therapies. This review will focus on the dynamic interconversion and overlap between different melanoma cell phenotypes in the context of therapy resistance and a dynamically changing multicellular microenvironment.
尽管丝裂原活化蛋白激酶（MAPK）和免疫检查点抑制剂在晚期黑色素瘤治疗中取得了近期的成功，但内在和获得性耐药机制决定了这些治疗方法的疗效。黑色素瘤的治疗耐药性不仅由基因进化驱动，还由表观遗传驱动的适应性可塑性驱动。黑色素瘤细胞在不同的转录程序、细胞周期状态和分化表型之间转换，反映出其具有高度动态的潜力，以适应包括免疫攻击或癌症治疗在内的各种外源性应激源。本综述将聚焦于在治疗耐药性和动态变化的多细胞微环境背景下，不同黑色素瘤细胞表型之间的动态相互转化和重叠。
