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