Targeting Transcription Factors for Cancer Treatment

Area of Science:

• Molecular Biology
• Oncology
• Drug Discovery

Background:

• Transcription factors play a crucial role in human diseases, particularly cancers, accounting for approximately 20% of identified oncogenes.
• Historically, transcription factors, excluding ligand-inducible nuclear receptors, were considered undruggable targets for therapeutic intervention.

Purpose of the Study:

• To review and discuss novel strategies for targeting transcription factors in cancer models.
• To highlight the impact of recent advances in understanding transcription factor biology on therapeutic development.

Main Methods:

• Modulating transcription factor expression or degradation.
• Inhibiting protein-protein interactions involving transcription factors.
• Developing small molecules to block transcription factor DNA binding through specific pockets or DNA-interacting sites.

Main Results:

• Several strategies for targeting transcription factors are effective in cancer models.
• Some targeted inhibitors are currently in clinical use or evaluation for cancer treatment.
• Modern chemistry and new technologies facilitate the development of specific inhibitors and improve understanding of pathological roles.

Conclusions:

• Advances in knowledge of transcription factor structure, function, and dynamics have transformed them into druggable targets.
• Targeting transcription factors offers promising avenues for improved cancer therapy and therapeutic control of oncogenic functions.