Downregulation of N-myc oncogene expression as a therapeutic strategy for childhood neuroblastoma.

神经母细胞瘤是幼儿常见的癌症，尽管使用强效抗癌药物治疗其他儿童癌症，但只有40%的存活率。许多实验室已经表明，最具侵略性的神经母细胞瘤肿瘤，对抗癌药物的作用最具抵抗力，具有异常数量的癌症相关基因，称为N-myc。具有多个N-myc拷贝的肿瘤患者的生存前景黯淡，迫切需要针对此类患者的新治疗方法。几项使用实验室中生长的神经母细胞瘤细胞模型的研究表明，有可能创造出可以特异性关闭N-myc基因的遗传物质小片段。当这种情况发生时，神经母细胞瘤细胞表现出较低的侵略性和恶性程度。我们最近已经证明，这些基因片段能够减少小鼠肿瘤的生长，这些小鼠已经被遗传操作以发展成神经细胞瘤。我们现在希望开发新型的基因片段（DNA酶），它们在关闭N-myc和抑制神经母细胞瘤发展方面将更加有效，因为这些片段可能对治疗患者的神经母细胞瘤非常有价值。

Neuroblastoma is a common cancer of young children which, despite the use of powerful anticancer drugs that cure other childhood cancers, has only a 40% survival rate. Many laboratories have shown that the most aggressive neuroblastoma tumours, which are most resistant to the action of anticancer drugs, have an abnormal number of copies of a cancer-associated gene, called N-myc. Patients whose tumours have multiple N-myc copies have dismal survival prospects, and new treatments for such patients are urgently needed. Several studies, using models of neuroblastoma cells growing in the laboratory, have shown that it is possible to create small fragments of genetic material which can specifically switch off the N-myc gene. When this happens, the neuroblastoma cells behave in a less aggressive and malignant way. We have recently shown that these genetic fragments are capable of reducing the growth of tumours in mice which have been genetically manipulated to develop neuroblastoma. We now want to develop new types of genetic fragments (DNAzymes) that will be even more effective at switching off N-myc and inhibiting neuroblastoma development, because these fragments may be extremely valuable for treating neuroblastoma in patients.