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
[11]   A bivalent chromatin structure marks key developmental genes in embryonic stem cells [J].
Bernstein, BE ;
Mikkelsen, TS ;
Xie, XH ;
Kamal, M ;
Huebert, DJ ;
Cuff, J ;
Fry, B ;
Meissner, A ;
Wernig, M ;
Plath, K ;
Jaenisch, R ;
Wagschal, A ;
Feil, R ;
Schreiber, SL ;
Lander, ES .
CELL, 2006, 125 (02) :315-326
[12]   The mammalian epigenome [J].
Bernstein, Bradley E. ;
Meissner, Alexander ;
Lander, Eric S. .
CELL, 2007, 128 (04) :669-681
[13]   Concentrations of the DNA methyltransferase inhibitor 5-fluoro-2′-deoxycytidine (FdCyd) and its cytotoxic metabolites in plasma of patients treated with FdCyd and tetrahydrouridine (THU) [J].
Beumer, Jan H. ;
Parise, Robert A. ;
Newman, Edward M. ;
Doroshow, James H. ;
Synold, Timothy W. ;
Lenz, Heinz-Josef ;
Egorin, Merrill J. .
CANCER CHEMOTHERAPY AND PHARMACOLOGY, 2008, 62 (02) :363-368
[14]   Reprogramming towards pluripotency requires AID-dependent DNA demethylation [J].
Bhutani, Nidhi ;
Brady, Jennifer J. ;
Damian, Mara ;
Sacco, Alessandra ;
Corbel, Stephane Y. ;
Blau, Helen M. .
NATURE, 2010, 463 (7284) :1042-U57
[15]   DNA methylation patterns and epigenetic memory [J].
Bird, A .
GENES & DEVELOPMENT, 2002, 16 (01) :6-21
[16]   Phase I study of decitabine alone or in combination with valproic acid in acute myeloid leukemia [J].
Blum, William ;
Klisovic, Rebecca B. ;
Hackanson, Bjoern ;
Liu, Zhongfa ;
Liu, Shujun ;
Devine, Hollie ;
Vukosavljevic, Tamara ;
Huynh, Lenguyen ;
Lozanski, Gerard ;
Kefauver, Cheryl ;
Plass, Christoph ;
Devine, Steven M. ;
Heerema, Nyla A. ;
Murgo, Anthony ;
Chan, Kenneth K. ;
Grever, Michael R. ;
Byrd, John C. ;
Marcucci, Guido .
JOURNAL OF CLINICAL ONCOLOGY, 2007, 25 (25) :3884-3891
[17]   Anticancer activities of histone deacetylase inhibitors [J].
Bolden, Jessica E. ;
Peart, Melissa J. ;
Johnstone, Ricky W. .
NATURE REVIEWS DRUG DISCOVERY, 2006, 5 (09) :769-784
[18]   Rational Combinations Using HDAC Inhibitors [J].
Bots, Michael ;
Johnstone, Ricky W. .
CLINICAL CANCER RESEARCH, 2009, 15 (12) :3970-3977
[19]   Vorinostat in Advanced Prostate Cancer Patients Progressing on Prior Chemotherapy (National Cancer Institute Trial 6862) Trial Results and Interleukin-6 Analysis: A study by the Department of Defense Prostate Cancer Clinical Trial Consortium and University of Chicago Phase 2 Consortium [J].
Bradley, Deborah ;
Rathkopf, Dana ;
Dunn, Rodney ;
Stadler, Walter M. ;
Liu, Glenn ;
Smith, David C. ;
Pili, Roberto ;
Zwiebel, James ;
Scher, Howard ;
Hussain, Maha .
CANCER, 2009, 115 (23) :5541-5549
[20]   HDACi - Targets beyond chromatin [J].
Buchwald, Marc ;
Kraemer, Oliver H. ;
Heinzel, Thorsten .
CANCER LETTERS, 2009, 280 (02) :160-167