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A New Way Forward in Cancer Drug Discovery: Inhibiting the SWI/SNF Chromatin Remodelling Complex

Giovanna Zinzalla1

  • 1Microbiology, Tumour and Cell Biology (MTC), and Science for Life Laboratory (SciLifeLab), Karolinska Institutet, Tomtebodavägen 23A, Stockholm, 171 65, Sweden. giovanna.zinzalla@ki.se.

Chembiochem : a European Journal of Chemical Biology
|December 20, 2015
PubMed

Insights

The SWI/SNF chromatin remodelling complex, implicated in 20% of cancers, paradoxically drives tumor growth in some cancers. Targeting its protein interactions offers a novel anticancer strategy.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Epigenetics

Background:

  • The SWI/SNF chromatin remodelling complex is frequently mutated in human cancers.
  • While often considered a tumor suppressor, its role is complex, with gain-of-function mutations and wild-type activity driving certain cancers.

Purpose of the Study:

  • To explore the paradoxical role of the SWI/SNF complex in cancer.
  • To identify novel therapeutic strategies targeting the SWI/SNF complex.

Main Methods:

  • Analysis of SWI/SNF complex mutations across various human cancers.
  • Investigation of SWI/SNF complex's protein-protein interactions.

Main Results:

  • SWI/SNF mutations are present in 20% of human cancers.
  • The wild-type SWI/SNF complex actively drives tumor progression in pancreatic cancer, leukemia, and breast cancer.
  • The complex engages in critical protein-protein interactions within itself and with transcription factors.

Conclusions:

  • The SWI/SNF complex presents a paradoxical role in cancer, acting as both a suppressor and a driver.
  • Targeting protein-protein interactions of the SWI/SNF complex is a promising strategy for developing selective anticancer agents.
Keywords:
SWI/SNF complexescancerepigeneticstranscription factors

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