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抗有丝分裂药物:它们是癌症治疗的新兴分子吗?

Anti-mitotic agents: Are they emerging molecules for cancer treatment?

机构信息

Biotechnology Center of the Federal University of Rio Grande do Sul, Department of Molecular Biology and Biotechnology, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.

Biotechnology Center of the Federal University of Rio Grande do Sul, Department of Molecular Biology and Biotechnology, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.

出版信息

Pharmacol Ther. 2017 May;173:67-82. doi: 10.1016/j.pharmthera.2017.02.007. Epub 2017 Feb 4.

Abstract

Mutations in cancer cells frequently result in cell cycle alterations that lead to unrestricted growth compared to normal cells. Considering this phenomenon, many drugs have been developed to inhibit different cell-cycle phases. Mitotic phase targeting disturbs mitosis in tumor cells, triggers the spindle assembly checkpoint and frequently results in cell death. The first anti-mitotics to enter clinical trials aimed to target tubulin. Although these drugs improved the treatment of certain cancers, and many anti-microtubule compounds are already approved for clinical use, severe adverse events such as neuropathies were observed. Since then, efforts have been focused on the development of drugs that also target kinases, motor proteins and multi-protein complexes involved in mitosis. In this review, we summarize the major proteins involved in the mitotic phase that can also be targeted for cancer treatment. Finally, we address the activity of anti-mitotic drugs tested in clinical trials in recent years.

摘要

癌细胞中的突变经常导致细胞周期的改变,使其与正常细胞相比无限制地生长。鉴于这一现象,已经开发出许多药物来抑制不同的细胞周期阶段。有丝分裂期靶向扰乱肿瘤细胞的有丝分裂,触发纺锤体组装检查点,并经常导致细胞死亡。第一批进入临床试验的抗有丝分裂药物旨在靶向微管蛋白。尽管这些药物改善了某些癌症的治疗效果,并且许多抗微管化合物已经获得临床批准,但还是观察到了严重的不良反应,如神经病变。从那时起,人们一直致力于开发靶向有丝分裂过程中涉及的激酶、马达蛋白和多蛋白复合物的药物。在这篇综述中,我们总结了参与有丝分裂阶段的主要蛋白质,这些蛋白质也可以作为癌症治疗的靶点。最后,我们讨论了近年来在临床试验中测试的抗有丝分裂药物的活性。

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