Enhancer reprogramming: critical roles in cancer and promising therapeutic strategies

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-...

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Main 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
Format: Article
Language:English
Published: Nature Publishing Group 2025-03-01
Series:Cell Death Discovery
Online Access:https://doi.org/10.1038/s41420-025-02366-3
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author Jinshou Yang
Feihan Zhou
Xiyuan Luo
Yuan Fang
Xing Wang
Xiaohong Liu
Ruiling Xiao
Decheng Jiang
Yuemeng Tang
Gang Yang
Lei You
Yupei Zhao
author_facet Jinshou Yang
Feihan Zhou
Xiyuan Luo
Yuan Fang
Xing Wang
Xiaohong Liu
Ruiling Xiao
Decheng Jiang
Yuemeng Tang
Gang Yang
Lei You
Yupei Zhao
author_sort Jinshou Yang
collection DOAJ
description 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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institution DOAJ
issn 2058-7716
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publishDate 2025-03-01
publisher Nature Publishing Group
record_format Article
series Cell Death Discovery
spelling doaj-art-b5269109a91b424bb4fc206f4d853ff12025-08-20T03:05:52ZengNature Publishing GroupCell Death Discovery2058-77162025-03-0111113010.1038/s41420-025-02366-3Enhancer reprogramming: critical roles in cancer and promising therapeutic strategiesJinshou Yang0Feihan Zhou1Xiyuan Luo2Yuan Fang3Xing Wang4Xiaohong Liu5Ruiling Xiao6Decheng Jiang7Yuemeng Tang8Gang Yang9Lei You10Yupei Zhao11Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical SciencesDepartment of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical SciencesDepartment of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical SciencesDepartment of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical SciencesDepartment of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical SciencesDepartment of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical SciencesDepartment of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical SciencesDepartment of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical SciencesDepartment of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical SciencesDepartment of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical SciencesDepartment of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical SciencesDepartment of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical SciencesAbstract 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.https://doi.org/10.1038/s41420-025-02366-3
spellingShingle Jinshou Yang
Feihan Zhou
Xiyuan Luo
Yuan Fang
Xing Wang
Xiaohong Liu
Ruiling Xiao
Decheng Jiang
Yuemeng Tang
Gang Yang
Lei You
Yupei Zhao
Enhancer reprogramming: critical roles in cancer and promising therapeutic strategies
Cell Death Discovery
title Enhancer reprogramming: critical roles in cancer and promising therapeutic strategies
title_full Enhancer reprogramming: critical roles in cancer and promising therapeutic strategies
title_fullStr Enhancer reprogramming: critical roles in cancer and promising therapeutic strategies
title_full_unstemmed Enhancer reprogramming: critical roles in cancer and promising therapeutic strategies
title_short Enhancer reprogramming: critical roles in cancer and promising therapeutic strategies
title_sort enhancer reprogramming critical roles in cancer and promising therapeutic strategies
url https://doi.org/10.1038/s41420-025-02366-3
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