Epigenetic therapy for solid tumors: from bench science to clinical trials.
The cancer epigenome is characterized by global DNA methylation and chromatin changes, such as the hypermethylation of specific CpG island promoters. Epigenetic agents like DNA methyltransferase or histone deacetylase inhibitors induce phenotype changes by reactivation of epigenetically silenced tumor suppressor genes. Despite initial promise in hematologic malignancies, epigenetic agents have not shown significant efficacy as monotherapy against solid tumors. Recent trials showed that epigenetic agents exert favorable modifier effects when combined with chemotherapy, hormonal therapy, or other epigenetic agents. Due to the novel nature of their mechanism, it is important to reconsider the optimal patient selection, drug regimen, study design, and outcome measures when pursuing future trials in order to discover the full potential of this new therapeutic modality.
Department of Surgery, George Washington University Medical Center, 2150 Pennsylvania Ave. NW, Suite 6B, Washington, DC 20037, USA.
Yen-Yi
YY
Juo
Xue-Jun
XJ
Gong
Ankita
A
Mishra
Xiao
X
Cui
Stephen B
SB
Baylin
Nilofer S
NS
Azad
Nita
N
Ahuja
D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D019175:DNA Methylation / Q000187:drug effects; D044127:Epigenesis, Genetic / Q000187:drug effects*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics
D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors
DNA methyltransferase inhibitor; cancer therapy; clinical trials; epigenetics; histone deacetylase inhibitor; solid tumor