a Department of Pathology , University of Colorado Denver, Anschutz Medical Campus , Aurora , CO , USA.
b Department of Pediatrics , University of Colorado Denver, Anschutz Medical Campus , Aurora , CO , USA.
Expert Opin Ther Targets. 2019 Apr;23(4):267-280. doi: 10.1080/14728222.2019.1580692. Epub 2019 Feb 26.
Epigenetic mechanisms of gene regulatory control play fundamental roles in developmental morphogenesis, and, as more recently appreciated, are heavily implicated in the onset and progression of neoplastic disease, including cancer. Many epigenetic mechanisms are therapeutically targetable, providing additional incentive for understanding of their contribution to cancer and other types of neoplasia. Areas covered: The Jumonji-domain histone demethylase (JHDM) family exemplifies many of the above traits. This review summarizes the current state of knowledge of the functions and pharmacologic targeting of JHDMs in cancer and other neoplastic processes, with an emphasis on diseases affecting the pediatric population. Expert opinion: To date, the JHDM family has largely been studied in the context of normal development and adult cancers. In contrast, comparatively few studies have addressed JHDM biology in cancer and other neoplastic diseases of childhood, especially solid (non-hematopoietic) neoplasms. Encouragingly, the few available examples support important roles for JHDMs in pediatric neoplasia, as well as potential roles for JHDM pharmacologic inhibition in disease management. Further investigations of JHDMs in cancer and other types of neoplasia of childhood can be expected to both enlighten disease biology and inform new approaches to improve disease outcomes.
基因调控的表观遗传机制在发育形态发生中起着基本作用,最近人们越来越认识到,它们在肿瘤疾病(包括癌症)的发生和进展中起着重要作用。许多表观遗传机制是可以治疗的靶点,这为了解它们在癌症和其他类型肿瘤中的作用提供了更多的动力。
组蛋白去甲基化酶(JHDM)家族中的 Jumonji 结构域就是一个很好的例子。这篇综述总结了目前关于 JHDM 在癌症和其他肿瘤过程中的功能和药物靶向的知识状况,重点是影响儿科人群的疾病。
迄今为止,JHDM 家族在正常发育和成人癌症的背景下进行了大量研究。相比之下,关于 JHDM 在儿童癌症和其他肿瘤性疾病中的生物学作用的研究相对较少,特别是在实体(非造血)肿瘤中。令人鼓舞的是,少数可用的例子支持 JHDM 在儿科肿瘤中的重要作用,以及 JHDM 药物抑制在疾病管理中的潜在作用。预计对儿童癌症和其他类型肿瘤中 JHDM 的进一步研究不仅可以阐明疾病生物学,还可以为改善疾病结局提供新的方法。