Partitioning of cancer therapeutics in nuclear condensates

doi:10.1126/science.aaz4427

GSTDTAP > 气候变化

DOI	10.1126/science.aaz4427
	Partitioning of cancer therapeutics in nuclear condensates
	Isaac A. Klein; Ann Boija; Lena K. Afeyan; Susana Wilson Hawken; Mengyang Fan; Alessandra Dall'Agnese; Ozgur Oksuz; Jonathan E. Henninger; Krishna Shrinivas; Benjamin R. Sabari; Ido Sagi; Victoria E. Clark; Jesse M. Platt; Mrityunjoy Kar; Patrick M. McCall; Alicia V. Zamudio; John C. Manteiga; Eliot L. Coffey; Charles H. Li; Nancy M. Hannett; Yang Eric Guo; Tim-Michael Decker; Tong Ihn Lee; Tinghu Zhang; Jing-Ke Weng; Dylan J. Taatjes; Arup Chakraborty; Phillip A. Sharp; Young Tae Chang; Anthony A. Hyman; Nathanael S. Gray; Richard A. Young
	2020-06-19
发表期刊	Science
出版年	2020
英文摘要	There is increasing interest in the function of phase-separated biomolecular condensates in cells because of their distinct properties and expanding roles in important biological processes. Klein et al. considered the fate of small-molecule therapeutics in the context of nuclear condensates (see the Perspective by Viny and Levine). They show that certain antineoplastic drugs have physicochemical properties that cause them to concentrate preferentially in condensates, both in vitro and in cancer cells. This property influences drug activity, and protein mutations that alter condensate formation can lead to drug resistance. Optimizing condensate partitioning may be valuable in developing improved therapeutics. Science , this issue p. [1386][1]; see also p. [1314][2] The nucleus contains diverse phase-separated condensates that compartmentalize and concentrate biomolecules with distinct physicochemical properties. Here, we investigated whether condensates concentrate small-molecule cancer therapeutics such that their pharmacodynamic properties are altered. We found that antineoplastic drugs become concentrated in specific protein condensates in vitro and that this occurs through physicochemical properties independent of the drug target. This behavior was also observed in tumor cells, where drug partitioning influenced drug activity. Altering the properties of the condensate was found to affect the concentration and activity of drugs. These results suggest that selective partitioning and concentration of small molecules within condensates contributes to drug pharmacodynamics and that further understanding of this phenomenon may facilitate advances in disease therapy. [1]: /lookup/doi/10.1126/science.aaz4427 [2]: /lookup/doi/10.1126/science.abc5318
领域	气候变化 ; 资源环境
URL	查看原文
引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/276703
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Isaac A. Klein,Ann Boija,Lena K. Afeyan,et al. Partitioning of cancer therapeutics in nuclear condensates[J]. Science,2020.
APA	Isaac A. Klein.,Ann Boija.,Lena K. Afeyan.,Susana Wilson Hawken.,Mengyang Fan.,...&Richard A. Young.(2020).Partitioning of cancer therapeutics in nuclear condensates.Science.
MLA	Isaac A. Klein,et al."Partitioning of cancer therapeutics in nuclear condensates".Science (2020).