Epigenetic therapies in patients with solid tumors: Focus on monotherapy with deoxyribonucleic acid methyltransferase inhibitors and histone deacetylase inhibitors

被引:12
作者
Rygiel, Katarzyna [1 ]
Bulas, Lucyna [2 ]
机构
[1] Med Univ Silesia SUM, Dept Family Practice, 3 Maja St 13-15, PL-41800 Zabrze, Poland
[2] Med Univ Silesia SUM, Dept Pharm, Katowice, Poland
关键词
Azacitidine; deoxyribonucleic acid methyltransferase inhibitors; epigenetic clinical studies; histone deacetylase inhibitors; solid tumors; vorinostat; PHASE-II TRIAL; SUBEROYLANILIDE HYDROXAMIC ACID; EPITHELIAL OVARIAN; CLINICAL-TRIAL; VALPROIC ACID; DOUBLE-BLIND; VORINOSTAT; CANCER; BELINOSTAT; RECURRENT;
D O I
10.4103/jcrt.JCRT_403_17
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Epigenomics is the study of the gene expression changes due to epigenetic processes and not due to the deoxyribonucleic acid (DNA) base sequence alterations. The key mechanisms of epigenetic regulation include DNA methylation, histone modifications, and noncoding RNAs. Epigenetic alterations in cancer are predominantly linked with hypermethylation of promoters of the tumor suppressor genes, global DNA hypomethylation, and increased expression of histone deacetylases (HDAC). There is a growing need to investigate epigenetic patterns and to provide safe and effective, innovative therapeutic strategies for oncology patients, who did not improve on traditional anticancer regimens. The epi-drugs (e.g., DNA methyltransferase inhibitors, e.g., azacitidine and decitabine and HDAC inhibitors, e.g., vorinostat and romidepsin) have been approved for the clinical use. In this paper, we provide a brief overview of the mechanisms of action and targets for novel epi-drugs, focusing on their potential clinical applications in patients with solid tumors, resistant to standard oncology treatments.
引用
收藏
页码:961 / 970
页数:10
相关论文
共 68 条
[1]   Phase I Trial of a New Schedule of Romidepsin in Patients with Advanced Cancers [J].
Amiri-Kordestani, Laleh ;
Luchenko, Victoria ;
Peer, Cody J. ;
Ghafourian, Kambiz ;
Reynolds, James ;
Draper, Deb ;
Frye, Robin ;
Woo, Sue ;
Venzon, David ;
Wright, John ;
Skarulis, Monica ;
Figg, William D. ;
Fojo, Tito ;
Bates, Susan E. ;
Piekarz, Richard L. .
CLINICAL CANCER RESEARCH, 2013, 19 (16) :4499-4507
[2]   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
[3]   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
[4]   When Signaling Kinases Meet Histones and Histone Modifiers in the Nucleus [J].
Baek, Sung Hee .
MOLECULAR CELL, 2011, 42 (03) :274-284
[5]   Epigenetic plasticity: A central regulator of epithelial-to-mesenchymal transition in cancer [J].
Bedi, Upasana ;
Mishra, Vivek Kumar ;
Wasilewski, David ;
Scheel, Christina ;
Johnsen, Steven A. .
ONCOTARGET, 2014, 5 (08) :2016-2029
[6]   Phase II trial of the histone deacetylase inhibitor vorinostat (Zolinza™, suberoylanilide hydroxamic acid, SAHA) in patients with recurrent and/or metastatic head and neck cancer [J].
Blumenschein, George R., Jr. ;
Kies, Merrill S. ;
Papadimitrakopoulou, Vassiliki A. ;
Lu, Charles ;
Kumar, Ashok J. ;
Ricker, Justin L. ;
Chiao, Judy H. ;
Chen, Cong ;
Frankel, Stanley R. .
INVESTIGATIONAL NEW DRUGS, 2008, 26 (01) :81-87
[7]   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
[8]   Phase I Study of Epigenetic Modulation with 5-Azacytidine and Valproic Acid in Patients with Advanced Cancers [J].
Braiteh, Fadi ;
Soriano, Andres O. ;
Garcia-Manero, Guillermo ;
Hong, David ;
Johnson, Marcella M. ;
Silva, Leandro De Padua ;
Yang, Hui ;
Alexander, Stefanie ;
Wolff, Johannes ;
Kurzrock, Razelle .
CLINICAL CANCER RESEARCH, 2008, 14 (19) :6296-6301
[9]   The quest for an effective and safe personalized cell therapy using epigenetic tools [J].
Brevini, T. A. L. ;
Pennarossa, G. ;
Manzoni, E. F. M. ;
Gandolfi, C. E. ;
Zenobi, A. ;
Gandolfi, F. .
CLINICAL EPIGENETICS, 2016, 8
[10]   A phase II trial of panobinostat in patients with advanced pretreated soft tissue sarcoma. A study from the French Sarcoma Group [J].
Cassier, P. A. ;
Lefranc, A. ;
Amela, E. Y. ;
Chevreau, C. ;
Bui, B. N. ;
Lecesne, A. ;
Ray-Coquard, I. ;
Chabaud, S. ;
Penel, N. ;
Berge, Y. ;
Domont, J. ;
Italiano, A. ;
Duffaud, F. ;
Cadore, A-C ;
Polivka, V. ;
Blay, J-Y .
BRITISH JOURNAL OF CANCER, 2013, 109 (04) :909-914