Partitioning of cancer therapeutics in nuclear condensates

Partitioning of cancer therapeutics in nuclear condensates

© 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works The nucleus contains diverse phase-separated condensates that compartmentalize and concentrate biomolecules with distinct physicochemical prope...

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Bibliographic Details
Main Authors: Klein, Isaac A., Boija, Ann, Afeyan, Lena K., Hawken, Susana Wilson, Fan, Mengyang, Dall'Agnese, Alessandra, Oksuz, Ozgur, Henninger, Jonathan E., Shrinivas, Krishna, Sabari, Benjamin R., Sagi, Ido, Clark, Victoria E., Platt, Jesse M., Kar, Mrityunjoy, McCall, Patrick M., Zamudio, Alicia V., Manteiga, John C., Coffey, Eliot L., Li, Charles H., Hannett, Nancy M., Guo, Yang Eric, Decker, Tim-Michael, Lee, Tong Ihn, Zhang, Tinghu, Weng, Jing-Ke, Taatjes, Dylan J., Chakraborty, Arup, Sharp, Phillip A., Chang, Young Tae, Hyman, Anthony A., Gray, Nathanael S., Young, Richard A.
Other Authors: Whitehead Institute for Biomedical Research
Format: Article
Language:English
Published: American Association for the Advancement of Science (AAAS) 2022
Online Access:https://hdl.handle.net/1721.1/135217.2
Description
Summary:© 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works 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.

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