Perturbing Enhancer Activity in Cancer Therapy

Area of Science:

• Genomics
• Cancer Biology
• Molecular Therapeutics

Background:

• Gene transcription regulation is crucial for development and homeostasis.
• Enhancers, distal regulatory genomic elements, are vital for specific gene expression and often dysregulated in cancer.
• Targeting enhancer-driven malignant dependencies is a promising therapeutic strategy.

Purpose of the Study:

• To review features making enhancers attractive cancer therapy targets.
• To discuss strategies for overcoming enhancer perturbation in cancer.
• To explore the potential of enhancer RNA (eRNA) as a biomarker for therapy response.

Main Methods:

• Review of recent studies on enhancer-driven cancer dependencies.
• Analysis of existing and emerging therapeutic approaches targeting enhancers.
• Discussion of biomarker potential for enhancer RNA (eRNA).

Main Results:

• Enhancers possess features amenable to targeted cancer therapy.
• Approved drugs and novel agents like BET inhibitors and CDK modulators impact enhancer activity.
• Enhancer RNA (eRNA) expression shows potential as a predictive biomarker for therapy response.

Conclusions:

• Targeting enhancers offers a promising avenue for precision oncology.
• Overcoming enhancer perturbation requires diverse therapeutic strategies.
• eRNA monitoring could enable patient stratification and personalized enhancer-targeted cancer treatments.