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. HannettYang 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

Research output: Contribution to journalArticlepeer-review

240 Scopus citations


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.

Original languageEnglish
Pages (from-to)1386-1392
Number of pages7
Issue number6497
StatePublished - 19 Jun 2020
Externally publishedYes

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© 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works


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