Targeting DNA binding proteins for cancer therapy

Cancer Sci. 2020 Apr;111(4):1058-1064. doi: 10.1111/cas.14355. Epub 2020 Mar 24.

Abstract

Dysregulation or mutation of DNA binding proteins such as transcription factors (TFs) is associated with the onset and progression of various types of disease, including cancer. Alteration of TF activity occurs in numerous cancer tissues due to gene amplification, deletion, and point mutations, and epigenetic modification. Although cancer-associated TFs are promising targets for cancer therapy, development of drugs targeting these TFs has historically been difficult due to the lack of high-throughput screening methods. Recent advances in technology for identification and selective inhibition of DNA binding proteins enable cancer researchers to develop novel therapeutics targeting cancer-associated TFs. In the present review, we summarize known cancer-associated TFs according to cancer type and introduce recently developed high-throughput approaches to identify selective inhibitors of cancer-associated TFs.

Keywords: DNA binding protein; drug discovery; high-throughput screening; telomere; transcription factor.

Publication types

  • Review

MeSH terms

  • Binding Sites / genetics
  • DNA-Binding Proteins / antagonists & inhibitors
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / therapeutic use
  • Epigenesis, Genetic / genetics
  • Humans
  • Molecular Targeted Therapy*
  • Neoplasms / genetics*
  • Neoplasms / therapy
  • Protein Binding / drug effects
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / genetics*
  • Transcription Factors / therapeutic use

Substances

  • DNA-Binding Proteins
  • Transcription Factors