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以有丝分裂途径为内分泌相关癌症治疗的靶点。

Targeting mitotic pathways for endocrine-related cancer therapeutics.

作者信息

Agarwal Shivangi, Varma Dileep

机构信息

Department of Cell and Molecular BiologyFeinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.

Department of Cell and Molecular BiologyFeinberg School of Medicine, Northwestern University, Chicago, Illinois, USA

出版信息

Endocr Relat Cancer. 2017 Sep;24(9):T65-T82. doi: 10.1530/ERC-17-0080. Epub 2017 Jun 14.

DOI:10.1530/ERC-17-0080
PMID:28615236
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5557717/
Abstract

A colossal amount of basic research over the past few decades has provided unprecedented insights into the highly complex process of cell division. There is an ever-expanding catalog of proteins that orchestrate, participate and coordinate in the exquisite processes of spindle formation, chromosome dynamics and the formation and regulation of kinetochore microtubule attachments. Use of classical microtubule poisons has still been widely and often successfully used to combat a variety of cancers, but their non-selective interference in other crucial physiologic processes necessitate the identification of novel druggable components specific to the cell cycle/division pathway. Considering cell cycle deregulation, unscheduled proliferation, genomic instability and chromosomal instability as a hallmark of tumor cells, there lies an enormous untapped terrain that needs to be unearthed before a drug can pave its way from bench to bedside. This review attempts to systematically summarize the advances made in this context so far with an emphasis on endocrine-related cancers and the avenues for future progress to target mitotic mechanisms in an effort to combat these dreadful cancers.

摘要

在过去几十年里,大量的基础研究为深入了解高度复杂的细胞分裂过程提供了前所未有的见解。参与纺锤体形成、染色体动态变化以及动粒微管附着的形成与调控等精细过程的蛋白质种类不断增加。经典的微管毒素仍被广泛且经常成功地用于对抗多种癌症,但其对其他关键生理过程的非选择性干扰,使得有必要鉴定细胞周期/分裂途径特有的新型可成药成分。鉴于细胞周期失调、异常增殖、基因组不稳定和染色体不稳定是肿瘤细胞的标志,在药物从实验室走向临床应用之前,仍有大量未开发的领域有待探索。本综述试图系统总结迄今为止在这方面取得的进展,重点关注内分泌相关癌症以及未来针对有丝分裂机制以对抗这些可怕癌症的进展途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc9d/5557717/df6100ddb29e/nihms888859f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc9d/5557717/df6100ddb29e/nihms888859f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc9d/5557717/df6100ddb29e/nihms888859f1.jpg

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本文引用的文献

1
Mechanisms of Chromosome Congression during Mitosis.有丝分裂期间染色体排列到赤道板的机制。
Biology (Basel). 2017 Feb 17;6(1):13. doi: 10.3390/biology6010013.
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Anti-mitotic agents: Are they emerging molecules for cancer treatment?抗有丝分裂药物:它们是癌症治疗的新兴分子吗?
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Centromere and kinetochore gene misexpression predicts cancer patient survival and response to radiotherapy and chemotherapy.着丝粒和动粒基因表达异常可预测癌症患者的生存和对放化疗的反应。
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Tumor suppressor protein DAB2IP participates in chromosomal stability maintenance through activating spindle assembly checkpoint and stabilizing kinetochore-microtubule attachments.肿瘤抑制蛋白DAB2IP通过激活纺锤体组装检查点和稳定动粒-微管附着来参与维持染色体稳定性。
Nucleic Acids Res. 2016 Oct 14;44(18):8842-8854. doi: 10.1093/nar/gkw746. Epub 2016 Aug 27.
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Overexpression of centromere protein K (CENPK) in ovarian cancer is correlated with poor patient survival and associated with predictive and prognostic relevance.着丝粒蛋白K(CENPK)在卵巢癌中的过表达与患者生存率低相关,并具有预测和预后相关性。
PeerJ. 2015 Nov 5;3:e1386. doi: 10.7717/peerj.1386. eCollection 2015.
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Control of microtubule organization and dynamics: two ends in the limelight.控制微管组织和动力学:两个焦点。
Nat Rev Mol Cell Biol. 2015 Dec;16(12):711-26. doi: 10.1038/nrm4084. Epub 2015 Nov 12.
7
The Aurora B Kinase in Chromosome Bi-Orientation and Spindle Checkpoint Signaling.染色体双定向和纺锤体检查点信号传导中的极光激酶B
Front Oncol. 2015 Oct 16;5:225. doi: 10.3389/fonc.2015.00225. eCollection 2015.
8
Targeting the Mitotic Catastrophe Signaling Pathway in Cancer.靶向癌症中的有丝分裂灾难信号通路。
Mediators Inflamm. 2015;2015:146282. doi: 10.1155/2015/146282. Epub 2015 Sep 27.
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Targeted Knockdown of the Kinetochore Protein D40/Knl-1 Inhibits Human Cancer in a p53 Status-Independent Manner.靶向敲低动粒蛋白D40/Knl-1以一种不依赖p53状态的方式抑制人类癌症。
Sci Rep. 2015 Sep 8;5:13676. doi: 10.1038/srep13676.
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γ-Tubulin complexes in microtubule nucleation and beyond.微管成核及其他过程中的γ-微管蛋白复合体
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