Review
Version 1
Preserved in Portico This version is not peer-reviewed
Perturbing Enhancer Activity in Cancer Therapy
Version 1
: Received: 28 March 2019 / Approved: 30 March 2019 / Online: 30 March 2019 (08:33:07 CET)
A peer-reviewed article of this Preprint also exists.
Hamdan, F.H.; Johnsen, S.A. Perturbing Enhancer Activity in Cancer Therapy. Cancers 2019, 11, 634. Hamdan, F.H.; Johnsen, S.A. Perturbing Enhancer Activity in Cancer Therapy. Cancers 2019, 11, 634.
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.
Keywords
Enhancers; BET inhibitors; CDK7 inhibitors; HDAC inhibitors; Transcription factors; eRNAs; cancer
Subject
Medicine and Pharmacology, Oncology and Oncogenics
Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Comments (0)
We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.
Leave a public commentSend a private comment to the author(s)
* All users must log in before leaving a comment
