摘要
中枢神经系统(CNS)肿瘤是儿童和青少年中第二大流行癌症组合,但由于高强度非选择性标准疗法传递给未成熟的儿童,因此在儿童和青少年中占大多数儿童癌症相关死亡率和幸存者相当多的发病率神经系统结构正在发展。这些肿瘤起源于不同的年龄,在生命的不同时期,在不同的地点和不同的细胞环境中,具有不同的细胞类型来源,并且对经典的当前治疗方法具有不同的反应。人口统计学,放射学和形态学表征具有几个局限性,将经典盒子放入不同种类的肿瘤中,这些肿瘤的遗传和表观遗传背景各不相同,并且可能在生物学上有所不同。鉴于后生破坏(即DNA甲基化,组蛋白修饰和染色质重塑)是儿科癌症中越来越频繁发现的共同特征,因此推测询问表观遗传标记可能有助于进一步确定分子谱,从而推测肿瘤生物学,进化和治疗这些肿瘤。融合传统特征和遗传和表观遗传特异性标记的综合方法为风险分层和更好的预测提供了巨大的前景。此外,这将有助于揭示肿瘤形成的关键驱动器途径,并发现出现在发育中的大脑中的肿瘤的靶向治疗,促进早期识别治疗响应者并准确追踪疾病进展。在本文中,我们回顾了最具代表性的儿童脑肿瘤,其中表观遗传学改变已被确定为肿瘤发展,维持或进展中的起始或驾驶事件。
关键词: 表观遗传学,儿童,脑肿瘤,表观遗传中断,小儿癌症,靶向治疗
Current Cancer Drug Targets
Title:Epigenetics in Clinical Management of Children and Adolescents with Brain Tumors
Volume: 18 Issue: 1
关键词: 表观遗传学,儿童,脑肿瘤,表观遗传中断,小儿癌症,靶向治疗
摘要: Central nervous system (CNS) tumors represent the second most prevalent group of cancers in children and adolescents, yet account for the majority of childhood cancer-related deaths and considerable morbidity among survivors, due to high-intensity non-selective standard therapies delivered to immature nervous system structures undergoing development. These tumors arise at different ages –not infrequently very early in life-, in different locations and cellular contexts, have varied cell types of origin, and have heterogeneous responses to the “classic” current therapeutic approaches. Demographic, radiologic and morphological characterization have several limitations, putting into the “classic boxes” heterogeneous tumors that are diverse in their genetic and epigenetic background and that will likely behave biologically different. Given that, epigenetic disruption (i.e. DNA methylation, histone modification and chromatin remodeling) is a common feature identified more and more frequently in pediatric cancer, it is logical to speculate that interrogating epigenetic marks may help to further define the molecular profile, and therefore tumor biology, evolution and treatment of these tumors. An integrated approach that incorporates traditional features complemented with genetic and epigenenetic specific markers offers tremendous promise to “risk-group” stratification and better prognostication. Also, it will help unveil the key driver pathways for tumor formation and for the discovery of targeted therapy for neoplasms that appear in the developing brain, facilitating early identification of therapy responders and track accurately disease progression. In this paper, we reviewed the most representative pediatric brain tumors where epigenetic alterations have been identified as initiating or driving events in tumor development, maintenance or progression.
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Epigenetics in Clinical Management of Children and Adolescents with Brain Tumors, Current Cancer Drug Targets 2018; 18 (1) . https://dx.doi.org/10.2174/1568009617666170203164456
DOI https://dx.doi.org/10.2174/1568009617666170203164456 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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