Harnessing the potential of epigenetic therapy to target solid tumors

被引:111
作者
Ahuja, Nita [1 ]
Easwaran, Hariharan [1 ]
Baylin, Stephen B. [1 ]
机构
[1] Johns Hopkins Med Inst, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21205 USA
关键词
DNA METHYLATION; HISTONE DEACETYLASE; MYELODYSPLASTIC SYNDROMES; CHROMATIN PATTERN; CANCER EPIGENOME; GENE-EXPRESSION; CELL SIGNATURE; IDH2; MUTATIONS; BREAST-CANCER; IN-VIVO;
D O I
10.1172/JCI69736
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Epigenetic therapies may play a prominent role in the future management of solid tumors. This possibility is based on the clinical efficacy of existing drugs in treating defined hematopoietic neoplasms, paired with promising new data from preclinical and clinical studies that examined these agents in solid tumors. We suggest that current drugs may represent a targeted therapeutic approach for reprogramming solid tumor cells, a strategy that must be pursued in concert with the explosion in knowledge about the molecular underpinnings of normal and cancer epigenomes. We hypothesize that understanding targeted proteins in the context of their enzymatic and scaffolding functions and in terms of their interactions in complexes with proteins that are targets of new drugs under development defines the future of epigenetic therapies for cancer.
引用
收藏
页码:56 / 63
页数:8
相关论文
共 127 条
[1]   Mutations in epigenetic modifiers in the pathogenesis and therapy of acute myeloid leukemia [J].
Abdel-Wahab, Omar ;
Levine, Ross L. .
BLOOD, 2013, 121 (18) :3563-3572
[2]  
Allis C.D., 2006, Epigenetics
[3]  
[Anonymous], 2012, ADV HEMATOL
[4]   Epigenetic protein families: a new frontier for drug discovery [J].
Arrowsmith, Cheryl H. ;
Bountra, Chas ;
Fish, Paul V. ;
Lee, Kevin ;
Schapira, Matthieu .
NATURE REVIEWS DRUG DISCOVERY, 2012, 11 (05) :384-400
[5]   DNA Methylation Alterations Exhibit Intraindividual Stability and Interindividual Heterogeneity in Prostate Cancer Metastases [J].
Aryee, Martin J. ;
Liu, Wennuan ;
Engelmann, Julia C. ;
Nuhn, Philipp ;
Gurel, Meltem ;
Haffner, Michael C. ;
Esopi, David ;
Irizarry, Rafael A. ;
Getzenberg, Robert H. ;
Nelson, William G. ;
Luo, Jun ;
Xu, Jianfeng ;
Isaacs, William B. ;
Bova, G. Steven ;
Yegnasubramanian, Srinivasan .
SCIENCE TRANSLATIONAL MEDICINE, 2013, 5 (169)
[6]   The future of epigenetic therapy in solid tumours-lessons from the past [J].
Azad, Nilofer ;
Zahnow, Cynthia A. ;
Rudin, Charles M. ;
Baylin, Stephen B. .
NATURE REVIEWS CLINICAL ONCOLOGY, 2013, 10 (05) :256-266
[7]   Dnmt3a and Dnmt3b are transcriptional repressors that exhibit unique localization properties to heterochromatin [J].
Bachman, KE ;
Rountree, MR ;
Baylin, SB .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (34) :32282-32287
[8]   Epigenetic Changes in Ovarian Cancer [J].
Balch, Curt ;
Fang, Fang ;
Matei, Daniela E. ;
Huang, Tim H. -M. ;
Nephew, Kenneth P. .
ENDOCRINOLOGY, 2009, 150 (09) :4003-4011
[9]   Nucleosome-Interacting Proteins Regulated by DNA and Histone Methylation [J].
Bartke, Till ;
Vermeulen, Michiel ;
Xhemalce, Blerta ;
Robson, Samuel C. ;
Mann, Matthias ;
Kouzarides, Tony .
CELL, 2010, 143 (03) :470-484
[10]   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