TY - JOUR
T1 - Epigenetic therapeutics
T2 - A new weapon in the war against cancer
AU - Ahuja, Nita
AU - Sharma, Anup R.
AU - Baylin, Stephen B.
N1 - Funding Information:
N.A. receives grant funding from Astex, Inc., and holds a patent on a methylation marker for pancreas cancer detection. S.B.B. consults for MDxHealth. MSP is licensed to MDxHealth in agreement with Johns Hopkins University (JHU), and S.B.B. and JHU are entitled to royalty shares received from sales. Portions of N.A.''s work cited in this invited review were supported by K23 CA127141 and R01 CA185357, both from the National Institutes of Health and National Cancer Institute, and by the American College of Surgeons. S.B.B.''s work is supported by grants ES011858 from the National Institutes of Environmental Health Sciences, W81XWH-14-1-0385 Teal from the US Department of Defense, SU2C-AACR-CT0109 from Stand Up 2Cancer-American Association for Cancer Research, the Miriam & Sheldon Adelson Medical Research Foundation, the Hodson Trust, and the Samuel Waxman Cancer Research Foundation. The authors thank Michael Ruiz and Kathy Bender for manuscript preparation.
Publisher Copyright:
© 2016 by Annual Reviews.
PY - 2016/1/14
Y1 - 2016/1/14
N2 - The past 15 years have seen an explosion of discoveries related to the cellular regulation of phenotypes through epigenetic mechanisms. This regulation provides a software that packages DNA, without changing the primary base sequence, to establish heritable patterns of gene expression. In cancer, many aspects of the epigenome, controlled by DNA methylation, chromatin, and nucleosome positioning, are altered as one means by which tumor cells maintain abnormal states of self-renewal at the expense of normal maturation. Epigenetic and genetic abnormalities thus collaborate in cancer initiation and progression, as exemplified by frequent mutations in genes encoding proteins that control the epigenome. There is growing emphasis on using epigenetic therapies to reprogram neoplastic cells toward a normal state. Many agents targeting epigenetic regulation are under development and entering clinical trials. This review highlights the promise that epigenetic therapy, often in combination with other therapies, will become a potent tool for cancer management over the next decade.
AB - The past 15 years have seen an explosion of discoveries related to the cellular regulation of phenotypes through epigenetic mechanisms. This regulation provides a software that packages DNA, without changing the primary base sequence, to establish heritable patterns of gene expression. In cancer, many aspects of the epigenome, controlled by DNA methylation, chromatin, and nucleosome positioning, are altered as one means by which tumor cells maintain abnormal states of self-renewal at the expense of normal maturation. Epigenetic and genetic abnormalities thus collaborate in cancer initiation and progression, as exemplified by frequent mutations in genes encoding proteins that control the epigenome. There is growing emphasis on using epigenetic therapies to reprogram neoplastic cells toward a normal state. Many agents targeting epigenetic regulation are under development and entering clinical trials. This review highlights the promise that epigenetic therapy, often in combination with other therapies, will become a potent tool for cancer management over the next decade.
KW - DNA methyltransferase inhibitor
KW - Epigenetics
KW - Histone deacetylase inhibitor therapy
UR - http://www.scopus.com/inward/record.url?scp=84954493378&partnerID=8YFLogxK
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U2 - 10.1146/annurev-med-111314-035900
DO - 10.1146/annurev-med-111314-035900
M3 - Article
C2 - 26768237
AN - SCOPUS:84954493378
SN - 0066-4219
VL - 67
SP - 73
EP - 89
JO - Annual review of medicine
JF - Annual review of medicine
ER -