Schramm Alexander, Lode Holger
a Pediatric Oncology and Hematology , University Children's Hospital Essen, University of Duisburg-Essen , Essen , Germany.
b Pediatric Oncology and Hematology , University Medicine Greifswald , Greifswald , Germany.
Hum Vaccin Immunother. 2016 Sep;12(9):2257-8. doi: 10.1080/21645515.2016.1171430. Epub 2016 Apr 20.
Amplification and concomitant overexpression of the MYCN oncogene is a frequent event in many malignancies including the childhood tumors, neuroblastoma and medulloblastoma. MYCN is only expressed in a defined time frame during early developmental processes, (1) which is beneficial for approaches combatting tumor-specific MYCN. However, MYCN is a transcription factors that was considered a poor drug target, until recent approaches suggested that down-regulation of MYCN could be possible by indirect targeting using Aurora kinase inhibitors or BET inhibitors. These concepts were proven using preclinical models (2-6) and are now entering clinical trials.
MYCN致癌基因的扩增及伴随的过表达在包括儿童肿瘤、神经母细胞瘤和髓母细胞瘤在内的许多恶性肿瘤中是常见事件。MYCN仅在早期发育过程中的特定时间框架内表达,这有利于对抗肿瘤特异性MYCN的方法。然而,MYCN是一种转录因子,曾被认为是一个较差的药物靶点,直到最近的研究表明,使用极光激酶抑制剂或BET抑制剂进行间接靶向可能会下调MYCN。这些概念已在临床前模型中得到验证(2 - 6),目前正在进入临床试验阶段。