拓扑异构酶和微管蛋白抑制剂:一种有希望的癌症治疗组合。

E Rudolf, M Cervinka
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引用次数: 14

摘要

现代治疗癌症的方法试图激活恶性细胞的内部自杀程序,从而有效地消除它们,而不涉及大多数其他身体系统。目前使用的许多细胞抑制剂都具有诱导细胞凋亡的作用,人们正在努力开发具有更好和更有效的促凋亡潜能的新细胞抑制剂。然而,尽管最近在这一领域取得了进展,仍然有许多恶性肿瘤表现出不同程度的细胞死亡抗性,这是由于信号通路的破坏和遗传改变,通常与增殖速度的增加有关。研究表明,拓扑异构酶抑制剂,如依托泊苷、喜树碱等,在实验和临床条件下是一种强大的、动态的细胞抑制剂。因此,它是一组由经典秋水仙碱和新型紫杉烷组成的微管靶向毒物。由于两组中的一些成员已被证明是通过不同的机制起作用的凋亡诱导剂,理论上它们的组合应该可以提高最终的治疗效果。这篇小型综述的重点是这种综合办法的可能性,以及这种战略可能带来的好处和危害。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Topoisomerases and tubulin inhibitors: a promising combination for cancer treatment.

Modern approaches to treatment of cancer seek to activate the internal suicide program in the malignant cells, and thereby effectively eliminate them without engaging most of other bodily systems. Many currently used cytostatics are known to induce apoptosis and efforts are being paid to develop new ones with better and more effective proapoptotic potential. Nevertheless, despite recent developments in this field, there are still numerous malignancies showing a varying degree of resistance to cell death due to the corrupted signaling pathways and genetic alterations, often in conjunction with expansive proliferation rate. It has been shown that topoisomerase inhibiting agents such as etoposide, camptothecin and others represent a powerful and dynamic group of cytostatic chemicals used in experimental and clinical conditions. So, it is a group of microtubule targeting poisons comprising classical colchicines on the one hand and new taxanes on the other hand. Since several members of both groups have been evidenced as apoptosis inducers operating via distinct mechanism, their combination should theoretically enhance the final therapeutic outcome. This minireview focuses on the possibilities of such a combinational approach with respect to possible benefits and hazards of this strategy.

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