@article{9a67c209fdd043d89c3b373909015063,
title = "Partitioning of cancer therapeutics in nuclear condensates",
abstract = "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.",
author = "Klein, {Isaac A.} and Ann Boija and Afeyan, {Lena K.} and Hawken, {Susana Wilson} and Mengyang Fan and Alessandra Dall'Agnese and Ozgur Oksuz and Henninger, {Jonathan E.} and Krishna Shrinivas and Sabari, {Benjamin R.} and Ido Sagi and Clark, {Victoria E.} and Platt, {Jesse M.} and Mrityunjoy Kar and McCall, {Patrick M.} and Zamudio, {Alicia V.} and Manteiga, {John C.} and Coffey, {Eliot L.} and Li, {Charles H.} and Hannett, {Nancy M.} and Guo, {Yang Eric} and Decker, {Tim Michael} and Lee, {Tong Ihn} and Tinghu Zhang and Weng, {Jing Ke} and Taatjes, {Dylan J.} and Arup Chakraborty and Sharp, {Phillip A.} and Chang, {Young Tae} and Hyman, {Anthony A.} and Gray, {Nathanael S.} and Young, {Richard A.}",
note = "Funding Information: We thank C. Glinkerman for helpful comments; W. Salmon of the W.M Keck Microscopy Facility and T. Volkert, J. Love, S. Mraz, and S. Gupta of the Whitehead Genome Technologies Core for technical assistance; and staff of the light microscopy facility at the MPI-CBG in Dresden for extensive help and support. This work was supported by NIH grants GM123511, CA213333, and CA155258 (R.A.Y.), NSF grant PHY1743900 (R.A.Y.), funds from Novo Nordisk (R.A.Y. and P.A.S.) NIH grant GM117370 (D.J.T.), Max Planck Society (A.A.H.), American Society of Clinical Oncology Young Investigator Award (I.A.K.), American Cancer Society Postdoctoral Fellowship (I.A.K.), Ovarian Cancer Research Alliance Mentored Investigator Award (I.A.K.), Swedish Research Council Postdoctoral Fellowship (VR 2017-00372) (A.B.), Hope Funds for Cancer Research (AD), Gruss-Lipper Postdoctoral Fellowship and by the Rothschild Postdoctoral Fellowship (I.S.), NIH grant T32:5T32DK007191-45 (J.M.P.), German Research Foundation DFG postdoctoral fellowship DE 3069/1-1 (T.-M.D.), Cancer Research Institute Irvington Fellowship (Y.E.G.), Damon Runyon Cancer Research Foundation Fellowship (2309-17) (BRS), ELBE postdoctoral fellowship (P.M.). Publisher Copyright: {\textcopyright} 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works",
year = "2020",
month = jun,
day = "19",
doi = "10.1126/science.aaz4427",
language = "English (US)",
volume = "368",
pages = "1386--1392",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6497",
}