Promises and challenges of anticancer drugs that target the epigenome

被引:0
作者
Verbrugge, Inge [1 ]
Johnstone, Ricky W. [1 ,2 ]
Bots, Michael [1 ]
机构
[1] Peter MacCallum Canc Ctr, Canc Therapeut Program, Melbourne, Vic 3002, Australia
[2] Univ Melbourne, Dept Pathol, Parkville, Vic 3010, Australia
基金
澳大利亚国家健康与医学研究理事会;
关键词
cancer; DNA methylation; epigenetics; histone modification; mouse models; personalized medicine; therapeutics; HISTONE DEACETYLASE INHIBITOR; REFRACTORY SOLID TUMORS; PHASE-II TRIAL; DNA METHYLTRANSFERASE INHIBITOR; SUBEROYLANILIDE HYDROXAMIC ACID; ACUTE MYELOID-LEUKEMIA; NATIONAL-CANCER-INSTITUTE; TRANS-RETINOIC ACID; DE-NOVO METHYLATION; CELL SELF-RENEWAL;
D O I
10.2217/EPI.11.82
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
The occurrence of epigenetic aberrations in cancer and their role in promoting tumorigenesis has led to the development of various small molecule inhibitors that target epigenetic enzymes. In preclinical settings, many epigenetic inhibitors demonstrate promising activity against a variety of both hematological and solid tumors. The therapeutic efficacy of those inhibitors that have entered the clinic however, is restricted predominantly to hematological malignancies. Here we outline the observed epigenetic aberrations in various types of cancer and the clinical responses to epigenetic drugs. We furthermore discuss strategies to improve the responsiveness of both hematological and solid malignancies to epigenetic drugs.
引用
收藏
页码:547 / 565
页数:19
相关论文
共 219 条
[1]   Revisiting the differentiation paradigm in acute promyelocytic leukemia [J].
Ablain, Julien ;
de The, Hugues .
BLOOD, 2011, 117 (22) :5795-5802
[2]   DOT1L, the H3K79 methyltransferase, is required for MLL-AF9-mediated leukemogenesis [J].
Anh Tram Nguyen ;
Taranova, Olena ;
He, Jin ;
Zhang, Yi .
BLOOD, 2011, 117 (25) :6912-6922
[3]   Phase I and pharmacodynamic trial of the DNA methyltransferase inhibitor decitabine and carboplatin in solid tumors [J].
Appleton, Kim ;
Mackay, Helen J. ;
Judson, Ian ;
Plumb, Jane A. ;
McCormick, Carol ;
Strathdee, Gordon ;
Lee, Chooi ;
Barrett, Sophie ;
Reade, Sarah ;
Jadayel, Dalal ;
Tang, Adrian ;
Bellenger, Katharine ;
Mackay, Lynsay ;
Setanoians, Albert ;
Schaetzlein, Andreas ;
Twelves, Chris ;
Kaye, Stanley B. ;
Brown, Robert .
JOURNAL OF CLINICAL ONCOLOGY, 2007, 25 (29) :4603-4609
[4]   Activity of decitabine, a hypomethylating agent, in chronic myelomonocytic leukemia [J].
Aribi, Ahmed ;
Borthakur, Gautam ;
Ravandi, Farhad ;
Shan, Jianqin ;
Davisson, Jan ;
Gortes, Jorge ;
Kantarjian, Hagop .
CANCER, 2007, 109 (04) :713-717
[5]   Phase I Study of Vorinostat in Combination with Bortezomib for Relapsed and Refractory Multiple Myeloma [J].
Badros, Ashraf ;
Burger, Angelika M. ;
Philip, Sunita ;
Niesvizky, Ruben ;
Kolla, Sarah S. ;
Goloubeva, Olga ;
Harris, Carolynn ;
Zwiebel, James ;
Wright, John J. ;
Espinoza-Delgado, Igor ;
Baer, Maria R. ;
Holleran, Julianne L. ;
Egorin, Merrill J. ;
Grant, Steven .
CLINICAL CANCER RESEARCH, 2009, 15 (16) :5250-5257
[6]   Chemoproteomics profiling of HDAC inhibitors reveals selective targeting of HDAC complexes [J].
Bantscheff, Marcus ;
Hopf, Carsten ;
Savitski, Mikhail M. ;
Dittmann, Antje ;
Grandi, Paola ;
Michon, Anne-Marie ;
Schlegl, Judith ;
Abraham, Yann ;
Becher, Isabelle ;
Bergamini, Giovanna ;
Boesche, Markus ;
Delling, Manja ;
Duempelfeld, Birgit ;
Eberhard, Dirk ;
Huthmacher, Carola ;
Mathieson, Toby ;
Poeckel, Daniel ;
Reader, Valerie ;
Strunk, Katja ;
Sweetman, Gavain ;
Kruse, Ulrich ;
Neubauer, Gitte ;
Ramsden, Nigel G. ;
Drewes, Gerard .
NATURE BIOTECHNOLOGY, 2011, 29 (03) :255-U124
[7]   Aberrant methylation of p16INK4a is an early event in lung cancer and a potential biomarker for early diagnosis [J].
Belinsky, SA ;
Nikula, KJ ;
Palmisano, WA ;
Michels, R ;
Saccomanno, G ;
Gabrielson, E ;
Baylin, SB ;
Herman, JG .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (20) :11891-11896
[8]   Combination Therapy with Vidaza and Entinostat Suppresses Tumor Growth and Reprograms the Epigenome in an Orthotopic Lung Cancer Model [J].
Belinsky, Steven A. ;
Grimes, Marcie J. ;
Picchi, Maria A. ;
Mitchell, Hugh D. ;
Stidley, Chris A. ;
Tesfaigzi, Yohannes ;
Channell, Meghan M. ;
Liu, Yanbin ;
Casero, Robert A., Jr. ;
Baylin, Stephen B. ;
Reed, Mathew D. ;
Tellez, Carmen S. ;
March, Thomas H. .
CANCER RESEARCH, 2011, 71 (02) :454-462
[9]   Acetylation inactivates the transcriptional repressor BCL6 [J].
Bereshchenko, OR ;
Gu, W ;
Dalla-Favera, R .
NATURE GENETICS, 2002, 32 (04) :606-613
[10]   An operational definition of epigenetics [J].
Berger, Shelley L. ;
Kouzarides, Tony ;
Shiekhattar, Ramin ;
Shilatifard, Ali .
GENES & DEVELOPMENT, 2009, 23 (07) :781-783