Using Chemistry to Target Neuroblastoma,ACS Chemical Neuroscience

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Using Chemistry to Target Neuroblastoma
ACS Chemical Neuroscience ( IF 4.1 ) Pub Date : 2017-08-24 00:00:00 , DOI: 10.1021/acschemneuro.7b00258
Jeanne N. Hansen ₁ , Xingguo Li ₁ , Y. George Zheng ₂ , Louis T. Lotta ₁ , Abhishek Dedhe ₁ , Nina F. Schor ₁

Affiliation

Neuroblastoma is a cancer of the neural crest almost exclusively seen in childhood. While children with single, small primary tumors are often cured with surgery alone, the 65% of children with neuroblastoma whose disease has metastasized have less than a 50% chance of surviving five years after diagnosis. Innovative pharmacological strategies are critically needed for these children. Efforts to identify novel targets that afford ablation of neuroblastoma with minimal toxicity to normal tissues are underway. Developing approaches to neuroblastoma include those that target the catecholamine transporter, ubiquitin E3 ligase, the ganglioside GD2, the retinoic acid receptor, the protein kinases ALK and Aurora, and protein arginine N-methyltransferases. Here, as examples of the use of chemistry to combat neuroblastoma, we describe targeting of the protein arginine N-methyltransferases and their role in prolonging the half-life of the neuroblastoma oncoprotein N-Myc, redox signaling in neuroblastoma, and developmentally regulated proteins expressed in primitive neuroblastoma cells but not in mature neural crest elements.

中文翻译：

使用化学方法靶向神经母细胞瘤

神经母细胞瘤是几乎在儿童时期才可见的神经c癌。患有单一，较小原发性肿瘤的儿童通常仅通过手术即可治愈，但65％的已转移疾病的成神经细胞瘤儿童在诊断后五年存活的机会不到50％。这些孩子迫切需要创新的药理策略。正在努力寻找能够消融对正常组织毒性最小的神经母细胞瘤的新型靶标。正在开发的神经母细胞瘤方法包括靶向儿茶酚胺转运蛋白，泛素E3连接酶，神经节苷脂GD2，视黄酸受体，蛋白激酶ALK和Aurora以及精氨酸N的方法。-甲基转移酶。在这里，作为使用化学方法对抗神经母细胞瘤的实例，我们描述了靶向蛋白精氨酸N-甲基转移酶及其在延长神经母细胞瘤癌蛋白N-Myc的半衰期，神经母细胞瘤中的氧化还原信号传导以及表达的发育调控蛋白中的作用在原始的神经母细胞瘤细胞中，但在成熟的神经c元件中没有。

更新日期：2017-08-25

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