Nüesch Jürg P F, Rommelaere Jean
Program "Infection and Cancer", Division Tumor Virology (F010), Deutsches Krebsforschungszentrum/German Cancer Research Center (DKFZ), Im Neuenheimer Feld 242, D-69120, Heidelberg, Germany,
Adv Exp Med Biol. 2014;818:99-124. doi: 10.1007/978-1-4471-6458-6_5.
Cancer chemotherapy with monospecific agents is often hampered by the rapid development of tumor resistance to the drug used. Therefore, combination treatments aiming at several different targets are sought. Viral regulatory proteins, modified or not, appear ideal for this purpose because of their multimodal killing action against neoplastically transformed cells. The large nonstructural protein NS1 of rodent parvoviruses is an excellent candidate for an anticancer agent, shown to interfere specifically with cancer cell growth and survival. The present review describes the structure, functions, and regulation of the multifunctional protein NS1, its specific interference with cell processes and cell protein activities, and what is known so far about the mechanisms underlying NS1 interference with cancer growth. It further outlines prospects for the development of new, multimodal cancer toxins and their potential applications.
使用单特异性药物的癌症化疗常常因肿瘤对所用药物迅速产生耐药性而受阻。因此，人们在寻求针对多个不同靶点的联合治疗方法。无论是否经过修饰，病毒调节蛋白因其对肿瘤转化细胞具有多模式杀伤作用，似乎是实现这一目的的理想选择。啮齿动物细小病毒的大型非结构蛋白NS1是一种抗癌剂的极佳候选物，已证明它能特异性干扰癌细胞的生长和存活。本综述描述了多功能蛋白NS1的结构、功能和调控，其对细胞过程和细胞蛋白活性的特异性干扰，以及目前已知的NS1干扰癌症生长的潜在机制。它还概述了新型多模式癌症毒素的开发前景及其潜在应用。
