Targeting epigenetic regulators to overcome drug resistance in cancers

Drug resistance is mainly responsible for cancer recurrence and poor prognosis. Epigenetic regulation is a heritable change in gene expressions independent of nucleotide sequence changes. As the common epigenetic regulation mechanisms, DNA methylation, histone modification, and non-coding RNA regula...

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Published inSignal transduction and targeted therapy Vol. 8; no. 1; pp. 69 - 24
Main Authors Wang, Nan, Ma, Ting, Yu, Bin
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 17.02.2023
Nature Publishing Group
Subjects
631/154
631/92
Cancer Research
Cell Biology
DNA methylation
Drug Resistance
Epigenesis, Genetic - genetics
Epigenetics
Histone Demethylases - genetics
Histones
Histones - genetics
Humans
Internal Medicine
Jumonji Domain-Containing Histone Demethylases - genetics
Jumonji Domain-Containing Histone Demethylases - metabolism
Medicine
Medicine & Public Health
Neoplasms - drug therapy
Neoplasms - genetics
Nucleotide sequence
Oncology
Pathology
Review
Review Article
RNA modification
siRNA
Tumors
Online AccessGet full text

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Abstract Drug resistance is mainly responsible for cancer recurrence and poor prognosis. Epigenetic regulation is a heritable change in gene expressions independent of nucleotide sequence changes. As the common epigenetic regulation mechanisms, DNA methylation, histone modification, and non-coding RNA regulation have been well studied. Increasing evidence has shown that aberrant epigenetic regulations contribute to tumor resistance. Therefore, targeting epigenetic regulators represents an effective strategy to reverse drug resistance. In this review, we mainly summarize the roles of epigenetic regulation in tumor resistance. In addition, as the essential factors for epigenetic modifications, histone demethylases mediate the histone or genomic DNA modifications. Herein, we comprehensively describe the functions of the histone demethylase family including the lysine-specific demethylase family, the Jumonji C-domain-containing demethylase family, and the histone arginine demethylase family, and fully discuss their regulatory mechanisms related to cancer drug resistance. In addition, therapeutic strategies, including small-molecule inhibitors and small interfering RNA targeting histone demethylases to overcome drug resistance, are also described.
AbstractList Abstract Drug resistance is mainly responsible for cancer recurrence and poor prognosis. Epigenetic regulation is a heritable change in gene expressions independent of nucleotide sequence changes. As the common epigenetic regulation mechanisms, DNA methylation, histone modification, and non-coding RNA regulation have been well studied. Increasing evidence has shown that aberrant epigenetic regulations contribute to tumor resistance. Therefore, targeting epigenetic regulators represents an effective strategy to reverse drug resistance. In this review, we mainly summarize the roles of epigenetic regulation in tumor resistance. In addition, as the essential factors for epigenetic modifications, histone demethylases mediate the histone or genomic DNA modifications. Herein, we comprehensively describe the functions of the histone demethylase family including the lysine-specific demethylase family, the Jumonji C-domain-containing demethylase family, and the histone arginine demethylase family, and fully discuss their regulatory mechanisms related to cancer drug resistance. In addition, therapeutic strategies, including small-molecule inhibitors and small interfering RNA targeting histone demethylases to overcome drug resistance, are also described.
Drug resistance is mainly responsible for cancer recurrence and poor prognosis. Epigenetic regulation is a heritable change in gene expressions independent of nucleotide sequence changes. As the common epigenetic regulation mechanisms, DNA methylation, histone modification, and non-coding RNA regulation have been well studied. Increasing evidence has shown that aberrant epigenetic regulations contribute to tumor resistance. Therefore, targeting epigenetic regulators represents an effective strategy to reverse drug resistance. In this review, we mainly summarize the roles of epigenetic regulation in tumor resistance. In addition, as the essential factors for epigenetic modifications, histone demethylases mediate the histone or genomic DNA modifications. Herein, we comprehensively describe the functions of the histone demethylase family including the lysine-specific demethylase family, the Jumonji C-domain-containing demethylase family, and the histone arginine demethylase family, and fully discuss their regulatory mechanisms related to cancer drug resistance. In addition, therapeutic strategies, including small-molecule inhibitors and small interfering RNA targeting histone demethylases to overcome drug resistance, are also described.Drug resistance is mainly responsible for cancer recurrence and poor prognosis. Epigenetic regulation is a heritable change in gene expressions independent of nucleotide sequence changes. As the common epigenetic regulation mechanisms, DNA methylation, histone modification, and non-coding RNA regulation have been well studied. Increasing evidence has shown that aberrant epigenetic regulations contribute to tumor resistance. Therefore, targeting epigenetic regulators represents an effective strategy to reverse drug resistance. In this review, we mainly summarize the roles of epigenetic regulation in tumor resistance. In addition, as the essential factors for epigenetic modifications, histone demethylases mediate the histone or genomic DNA modifications. Herein, we comprehensively describe the functions of the histone demethylase family including the lysine-specific demethylase family, the Jumonji C-domain-containing demethylase family, and the histone arginine demethylase family, and fully discuss their regulatory mechanisms related to cancer drug resistance. In addition, therapeutic strategies, including small-molecule inhibitors and small interfering RNA targeting histone demethylases to overcome drug resistance, are also described.
Drug resistance is mainly responsible for cancer recurrence and poor prognosis. Epigenetic regulation is a heritable change in gene expressions independent of nucleotide sequence changes. As the common epigenetic regulation mechanisms, DNA methylation, histone modification, and non-coding RNA regulation have been well studied. Increasing evidence has shown that aberrant epigenetic regulations contribute to tumor resistance. Therefore, targeting epigenetic regulators represents an effective strategy to reverse drug resistance. In this review, we mainly summarize the roles of epigenetic regulation in tumor resistance. In addition, as the essential factors for epigenetic modifications, histone demethylases mediate the histone or genomic DNA modifications. Herein, we comprehensively describe the functions of the histone demethylase family including the lysine-specific demethylase family, the Jumonji C-domain-containing demethylase family, and the histone arginine demethylase family, and fully discuss their regulatory mechanisms related to cancer drug resistance. In addition, therapeutic strategies, including small-molecule inhibitors and small interfering RNA targeting histone demethylases to overcome drug resistance, are also described.
ArticleNumber 69
Author Ma, Ting
Wang, Nan
Yu, Bin
Author_xml – sequence: 1
  givenname: Nan
  surname: Wang
  fullname: Wang, Nan
  organization: Institute of Drug Discovery & Development, School of Pharmaceutical Sciences, Zhengzhou University
– sequence: 2
  givenname: Ting
  surname: Ma
  fullname: Ma, Ting
  email: mating@zzu.edu.cn
  organization: Institute of Drug Discovery & Development, School of Pharmaceutical Sciences, Zhengzhou University
– sequence: 3
  givenname: Bin
  orcidid: 0000-0002-0531-2236
  surname: Yu
  fullname: Yu, Bin
  email: yubin@zzu.edu.cn
  organization: Institute of Drug Discovery & Development, School of Pharmaceutical Sciences, Zhengzhou University
BackLink https://www.ncbi.nlm.nih.gov/pubmed/36797239$$D View this record in MEDLINE/PubMed
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Snippet Drug resistance is mainly responsible for cancer recurrence and poor prognosis. Epigenetic regulation is a heritable change in gene expressions independent of...
Abstract Drug resistance is mainly responsible for cancer recurrence and poor prognosis. Epigenetic regulation is a heritable change in gene expressions...
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StartPage 69
SubjectTerms 631/154
631/92
Cancer Research
Cell Biology
DNA methylation
Drug Resistance
Epigenesis, Genetic - genetics
Epigenetics
Histone Demethylases - genetics
Histones
Histones - genetics
Humans
Internal Medicine
Jumonji Domain-Containing Histone Demethylases - genetics
Jumonji Domain-Containing Histone Demethylases - metabolism
Medicine
Medicine & Public Health
Neoplasms - drug therapy
Neoplasms - genetics
Nucleotide sequence
Oncology
Pathology
Review
Review Article
RNA modification
siRNA
Tumors
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Title Targeting epigenetic regulators to overcome drug resistance in cancers
URI https://link.springer.com/article/10.1038/s41392-023-01341-7
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Volume 8
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