New anti-cancer strategies: epigenetic therapies and biomarkers.
Epigenetics is the study of chromatin modifications that affect gene expression without altering DNA nucleotide sequences. This review highlights a prominent role for epigenetic therapies, particularly those that reverse aberrant DNA methylation and histone acetylation, in the potential treatment of cancer. Administration of such therapies to reverse epigenetic "silencing" of tumor suppressors, including genes involved in chemotherapy responses, could prove useful in the management of cancer patients. In this review, we summarize recent advances in the use of methyltransferase and histone deacetylase inhibitors and possible synergistic combinations of these to achieve maximal tumor suppressor gene re-expression. Moreover, when used in combination with conventional chemotherapeutic agents, epigenetic-based therapies may provide a means to resensitize drug-resistant tumors to established treatments. As specific, aberrant epigenetic modifications are frequently associated with distinct cancer types, and likely occur early in tumorigenesis, these have potential utility as biomarkers. Finally, future directions are addressed, including alternative epigenetic targets, gene-specific modifications, and the use of bioinformatics.
Balch
Curtis
C
Medical Sciences, Indiana University, Bloomington, IN 47405, USA.
Montgomery
John S
JS
Paik
Hyun-Il
HI
Kim
Sun
S
Kim
Sun
S
Huang
Tim H-M
TH
Nephew
Kenneth P
KP
D000107:Acetylation; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D015415:Biomarkers; D019295:Computational Biology; D019175:DNA Methylation; D015195:Drug Design; D044127:Epigenesis, Genetic; D020868:Gene Silencing; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007167:Immunotherapy; D009369:Neoplasms / Q000628:therapy*
D000970:Antineoplastic Agents; D015415:Biomarkers; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006655:Histone Deacetylases