Enhancer Reprogramming: Critical Roles in Cancer and Promising Therapeutic Strategies

Overview

Journal Cell Death Discov

Date 2025 Mar 3

PMID 40032852

Authors

Jinshou Yang

Feihan Zhou

Xiyuan Luo

Yuan Fang

Xing Wang

Xiaohong Liu

Ruiling Xiao

Decheng Jiang

Yuemeng Tang

Gang Yang

Lei You

Yupei Zhao

Affiliations

Soon will be listed here.

Abstract

Transcriptional dysregulation is a hallmark of cancer initiation and progression, driven by genetic and epigenetic alterations. Enhancer reprogramming has emerged as a pivotal driver of carcinogenesis, with cancer cells often relying on aberrant transcriptional programs. The advent of high-throughput sequencing technologies has provided critical insights into enhancer reprogramming events and their role in malignancy. While targeting enhancers presents a promising therapeutic strategy, significant challenges remain. These include the off-target effects of enhancer-targeting technologies, the complexity and redundancy of enhancer networks, and the dynamic nature of enhancer reprogramming, which may contribute to therapeutic resistance. This review comprehensively encapsulates the structural attributes of enhancers, delineates the mechanisms underlying their dysregulation in malignant transformation, and evaluates the therapeutic opportunities and limitations associated with targeting enhancers in cancer.

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