Partitioning of cancer therapeutics in nuclear condensates. Journal Article uri icon

Overview

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.

publication date

  • June 19, 2020

has subject area

Date in CU Experts

  • July 1, 2020 12:29 PM

Full Author List

  • Klein IA; Boija A; Afeyan LK; Hawken SW; Fan M; Dall'Agnese A; Oksuz O; Henninger JE; Shrinivas K; Sabari BR

author count

  • 32

Other Profiles

Electronic International Standard Serial Number (EISSN)

  • 1095-9203

Additional Document Info

start page

  • 1386

end page

  • 1392

volume

  • 368

issue

  • 6497