Targeting epigenetic regulators for cancer therapy: mechanisms and advances in clinical trials

被引：713
作者：
Cheng, Yuan [1 ,2 ]
He, Cai [1 ,2 ]
Wang, Manni [1 ,2 ]
Ma, Xuelei [1 ,2 ]
Mo, Fei [1 ,2 ]
Yang, Shengyong [1 ,2 ]
Han, Junhong [1 ,2 ]
Wei, Xiawei [1 ,2 ]
机构：
[1] Sichuan Univ, West China Hosp, State Key Lab Biotherapy, Lab Aging Res & Canc Drug Target, Chengdu, Sichuan, Peoples R China
[2] Sichuan Univ, West China Hosp, Canc Ctr, Natl Clin Res Ctr Geriatr, Chengdu, Sichuan, Peoples R China
来源：
SIGNAL TRANSDUCTION AND TARGETED THERAPY | 2019年 / 4卷 / 1期
关键词：
ACUTE MYELOID-LEUKEMIA; CELL LUNG-CANCER; EPITHELIAL-MESENCHYMAL-TRANSITION; TUMOR-SUPPRESSOR GENE; HISTONE DEACETYLASE INHIBITORS; SMALL-MOLECULE INHIBITOR; DE-NOVO METHYLATION; MESSENGER-RNA EXPRESSION; PROTEIN ARGININE METHYLTRANSFERASE; RUBINSTEIN-TAYBI-SYNDROME;
D O I：
10.1038/s41392-019-0095-0
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Epigenetic alternations concern heritable yet reversible changes in histone or DNA modifications that regulate gene activity beyond the underlying sequence. Epigenetic dysregulation is often linked to human disease, notably cancer. With the development of various drugs targeting epigenetic regulators, epigenetic-targeted therapy has been applied in the treatment of hematological malignancies and has exhibited viable therapeutic potential for solid tumors in preclinical and clinical trials. In this review, we summarize the aberrant functions of enzymes in DNA methylation, histone acetylation and histone methylation during tumor progression and highlight the development of inhibitors of or drugs targeted at epigenetic enzymes.
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页数：39
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共 665 条
[31]   Nonclinical pharmacokinetics and metabolism of EPZ-5676, a novel DOT1L histone methyltransferase inhibitor [J].
Basavapathruni, Aravind ;
Olhava, Edward J. ;
Daigle, Scott R. ;
Therkelsen, Carly A. ;
Jin, Lei ;
Boriack-Sjodin, P. Ann ;
Allain, Christina J. ;
Klaus, Christine R. ;
Raimondi, Alejandra ;
Scott, Margaret Porter ;
Dovletoglou, Angelos ;
Richon, Victoria M. ;
Pollock, Roy M. ;
Copeland, Robert A. ;
Moyer, Mikel P. ;
Chesworth, Richard ;
Pearson, Paul G. ;
Waters, Nigel J. .
BIOPHARMACEUTICS & DRUG DISPOSITION, 2014, 35 (04) :237-252
[32]   Kaiso depletion attenuates the growth and survival of triple negative breast cancer cells [J].
Bassey-Archibong, Blessing I. ;
Rayner, Lyndsay G. A. ;
Hercules, Shawn M. ;
Aarts, Craig W. ;
Dvorkin-Gheva, Anna ;
Bramson, Jonathan L. ;
Hassell, John A. ;
Daniel, Juliet M. .
CELL DEATH & DISEASE, 2017, 8 :e2689-e2689
[33]   Downregulation of HDAC2 and HDAC3 via oleuropein as a potent prevention and therapeutic agent in MCF-7 breast cancer cells [J].
Bayat, Sahar ;
Derakhshan, Sima Mansoori ;
Derakhshan, Neda Mansoori ;
Khaniani, Mahmoud Shekari ;
Alivand, Mohammad Reza .
JOURNAL OF CELLULAR BIOCHEMISTRY, 2019, 120 (06) :9172-9180
[34]   Epigenetic gene silencing in cancer - a mechanism for early oncogenic pathway addiction? [J].
Baylin, SB ;
Ohm, JE .
NATURE REVIEWS CANCER, 2006, 6 (02) :107-116
[35]   A decade of exploring the cancer epigenome - biological and translational implications [J].
Baylin, Stephen B. ;
Jones, Peter A. .
NATURE REVIEWS CANCER, 2011, 11 (10) :726-734
[36]   SYNTHESIS AND ANTI-TUMOR ACTIVITY OF DIHYDRO-5-AZACYTIDINE, A HYDROLYTICALLY STABLE ANALOG OF 5-AZACYTIDINE [J].
BEISLER, JA ;
ABBASI, MM ;
KELLEY, JA ;
DRISCOLL, JS .
JOURNAL OF MEDICINAL CHEMISTRY, 1977, 20 (06) :806-812
[37]   CpG Island Methylation Profiling in Human Salivary Gland Adenoid Cystic Carcinoma [J].
Bell, Achim ;
Bell, Diana ;
Weber, Randal S. ;
El-Naggar, Adel K. .
CANCER, 2011, 117 (13) :2898-2909
[38]   Epigenetic crosstalk [J].
Ben-Porath, I ;
Cedar, H .
MOLECULAR CELL, 2001, 8 (05) :933-935
[39]   The methyl-CpG- binding protein MECP2 is required for prostate cancer cell growth [J].
Bernard, D ;
Gil, J ;
Dumont, P ;
Rizzo, S ;
Monté, D ;
Quatannens, B ;
Hudson, D ;
Visakorpi, T ;
Fuks, F ;
de Launoit, Y .
ONCOGENE, 2006, 25 (09) :1358-1366
[40]   MLL-Rearranged Leukemia Is Dependent on Aberrant H3K79 Methylation by DOT1L [J].
Bernt, Kathrin M. ;
Zhu, Nan ;
Sinha, Amit U. ;
Vempati, Sridhar ;
Faber, Joerg ;
Krivtsov, Andrei V. ;
Feng, Zhaohui ;
Punt, Natalie ;
Daigle, Amanda ;
Bullinger, Lars ;
Pollock, Roy M. ;
Richon, Victoria M. ;
Kung, Andrew L. ;
Armstrong, Scott A. .
CANCER CELL, 2011, 20 (01) :66-78
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