Targeting mitotic pathways for endocrine-related cancer therapeutics.
Targeting mitotic pathways for endocrine-related cancer therapeutics.
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DOI：
10.1530/erc-17-0080
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发表时间：
2017-09
影响因子：
3.9
通讯作者：
Varma D
中科院分区：
文献类型：
--
作者：
Agarwal S;Varma D
过去几十年进行的大量基础研究为高度复杂的细胞分裂过程提供了前所未有的见解。蛋白质目录不断扩大，它们编排、参与和协调纺锤体形成、染色体动力学以及动粒微管附着物的形成和调节的微妙过程。经典微管毒物的使用仍然被广泛且经常成功地用于对抗各种癌症，但它们对其他关键生理过程的非选择性干扰需要识别特定于细胞周期/分裂途径的新型可成药成分。考虑到细胞周期失调、非计划性增殖、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之前，还有一个巨大的未开发领域需要挖掘。这篇综述试图系统地总结迄今为止在这方面取得的进展，重点是内分泌相关的癌症以及针对有丝分裂机制以对抗这些可怕的癌症的未来进展的途径。
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 catalogue 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.