Partitioning of cancer therapeutics in nuclear condensates

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Isaac A. Klein - , Whitehead Institute for Biomedical Research, Harvard University (Author)
  • Ann Boija - , Whitehead Institute for Biomedical Research (Author)
  • Lena K. Afeyan - , Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology (MIT) (Author)
  • Susana Wilson Hawken - , Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology (MIT) (Author)
  • Mengyang Fan - , Dana-Farber Cancer Institute, Harvard University (Author)
  • Alessandra Dall'Agnese - , Whitehead Institute for Biomedical Research (Author)
  • Ozgur Oksuz - , Whitehead Institute for Biomedical Research (Author)
  • Jonathan E. Henninger - , Whitehead Institute for Biomedical Research (Author)
  • Krishna Shrinivas - , Massachusetts Institute of Technology (MIT) (Author)
  • Benjamin R. Sabari - , Whitehead Institute for Biomedical Research (Author)
  • Ido Sagi - , Whitehead Institute for Biomedical Research (Author)
  • Victoria E. Clark - , Whitehead Institute for Biomedical Research, Harvard University (Author)
  • Jesse M. Platt - , Whitehead Institute for Biomedical Research, Massachusetts General Hospital (Author)
  • Mrityunjoy Kar - , Max-Planck-Institute for the Physics of Complex Systems (Author)
  • Patrick M. McCall - , Max-Planck-Institute for the Physics of Complex Systems, Max Planck Institute of Molecular Cell Biology and Genetics, Center for Systems Biology Dresden (CSBD) (Author)
  • Alicia V. Zamudio - , Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology (MIT) (Author)
  • John C. Manteiga - , Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology (MIT) (Author)
  • Eliot L. Coffey - , Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology (MIT) (Author)
  • Charles H. Li - , Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology (MIT) (Author)
  • Nancy M. Hannett - , Whitehead Institute for Biomedical Research (Author)
  • Yang Eric Guo - , Whitehead Institute for Biomedical Research (Author)
  • Tim Michael Decker - , University of Colorado Boulder (Author)
  • Tong Ihn Lee - , Whitehead Institute for Biomedical Research (Author)
  • Tinghu Zhang - , Dana-Farber Cancer Institute, Harvard University (Author)
  • Jing Ke Weng - , Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology (MIT) (Author)
  • Dylan J. Taatjes - , University of Colorado Boulder (Author)
  • Arup Chakraborty - , Massachusetts Institute of Technology (MIT), Harvard University (Author)
  • Phillip A. Sharp - , Massachusetts Institute of Technology (MIT) (Author)
  • Young Tae Chang - , Pohang University of Science and Technology (Author)
  • Anthony A. Hyman - , Max Planck Institute of Molecular Cell Biology and Genetics, TUD Dresden University of Technology, Clusters of Excellence PoL: Physics of Life (Author)
  • Nathanael S. Gray - , Dana-Farber Cancer Institute, Harvard University (Author)
  • Richard A. Young - , Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology (MIT) (Author)

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.

Details

Original languageEnglish
Pages (from-to)1386-1392
Number of pages7
JournalScience
Volume368
Issue number6497
Publication statusPublished - 19 Jun 2020
Peer-reviewedYes

External IDs

PubMed 32554597

Keywords

Sustainable Development Goals

ASJC Scopus subject areas