The 3D Genome as a Target for Anticancer Therapy

Trends Mol Med. 2020 Feb;26(2):141-149. doi: 10.1016/j.molmed.2019.09.011. Epub 2019 Oct 31.

Abstract

The role of 3D genome organization in the precise regulation of gene expression is well established. Accordingly, the mechanistic connections between 3D genome alterations and disease development are becoming increasingly apparent. This opinion article provides a snapshot of our current understanding of the 3D genome alterations associated with cancers. We discuss potential connections of the 3D genome and cancer transcriptional addiction phenomenon as well as molecular mechanisms of action of 3D genome-disrupting drugs. Finally, we highlight issues and perspectives raised by the discovery of the first pharmaceutical strongly affecting 3D genome organization.

Keywords: 3D genome; CTCF; chromatin damage; curaxins; topologically associating domains (TADs); transcriptional addiction.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use*
  • Chromatin / genetics
  • DNA / genetics
  • Epigenomics / methods
  • Genome / genetics*
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / genetics*
  • Small Molecule Libraries / pharmacology
  • Small Molecule Libraries / therapeutic use
  • Transcription, Genetic / drug effects
  • Transcription, Genetic / genetics

Substances

  • Antineoplastic Agents
  • Chromatin
  • Small Molecule Libraries
  • DNA