Partitioning of cancer therapeutics in nuclear condensates. Academic 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.

authors

publication date

  • June 19, 2020

Research

keywords

  • Antineoplastic Agents
  • Cell Nucleus
  • Drug Resistance, Neoplasm
  • Neoplasms

Identity

PubMed Central ID

  • PMC7735713

Scopus Document Identifier

  • 85086725637

Digital Object Identifier (DOI)

  • 10.1126/science.aaz4427

PubMed ID

  • 32554597

Additional Document Info

volume

  • 368

issue

  • 6497