Perturbing enhancer activity in cancer therapy

Feda H. Hamdan, Steven Johnsen

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Tight regulation of gene transcription is essential for normal development, tissue homeostasis, and disease-free survival. Enhancers are distal regulatory elements in the genome that provide specificity to gene expression programs and are frequently misregulated in cancer. Recent studies examined various enhancer-driven malignant dependencies and identified different approaches to specifically target these programs. In this review, we describe numerous features that make enhancers good transcriptional targets in cancer therapy and discuss different approaches to overcome enhancer perturbation. Interestingly, a number of approved therapeutic agents, such as cyclosporine, steroid hormones, and thiazolidinediones, actually function by affecting enhancer landscapes by directly targeting very specific transcription factor programs. More recently, a broader approach to targeting deregulated enhancer programs has been achieved via Bromodomain and Extraterminal (BET) inhibition or perturbation of transcription-related cyclin-dependent kinases (CDK). One challenge to enhancer-targeted therapy is proper patient stratification. We suggest that monitoring of enhancer RNA (eRNA) expression may serve as a unique biomarker of enhancer activity that can help to predict and monitor responsiveness to enhancer-targeted therapies. A more thorough investigation of cancer-specific enhancers and the underlying mechanisms of deregulation will pave the road for an effective utilization of enhancer modulators in a precision oncology approach to cancer treatment.

Original languageEnglish (US)
Article number634
JournalCancers
Volume11
Issue number5
DOIs
StatePublished - May 1 2019

Fingerprint

Neoplasms
Therapeutics
Thiazolidinediones
Cyclin-Dependent Kinases
Cyclosporine
Disease-Free Survival
Homeostasis
Transcription Factors
Biomarkers
Steroids
Genome
Hormones
RNA
Gene Expression
Genes

Keywords

  • BET inhibitors
  • Cancer
  • CDK7 inhibitors
  • Enhancers
  • eRNAs
  • HDAC inhibitors
  • Transcription factors

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Perturbing enhancer activity in cancer therapy. / Hamdan, Feda H.; Johnsen, Steven.

In: Cancers, Vol. 11, No. 5, 634, 01.05.2019.

Research output: Contribution to journalArticle

Hamdan, Feda H. ; Johnsen, Steven. / Perturbing enhancer activity in cancer therapy. In: Cancers. 2019 ; Vol. 11, No. 5.
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