DNA Hypomethylating Drugs in Cancer Therapy.
Aberrant DNA methylation is a critically important modification in cancer cells, which, through promoter and enhancer DNA methylation changes, use this mechanism to activate oncogenes and silence of tumor-suppressor genes. Targeting DNA methylation in cancer using DNA hypomethylating drugs reprograms tumor cells to a more normal-like state by affecting multiple pathways, and also sensitizes these cells to chemotherapy and immunotherapy. The first generation hypomethylating drugs azacitidine and decitabine are routinely used for the treatment of myeloid leukemias and a next-generation drug (guadecitabine) is currently in clinical trials. This review will summarize preclinical and clinical data on DNA hypomethylating drugs as a cancer therapy.
Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.
Takahiro
T
Sato
Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.|Fox Chase Cancer Center, Temple Health, Philadelphia, Pennsylvania 19111.
Jean-Pierre J
JJ
Issa
Fox Chase Cancer Center, Temple Health, Philadelphia, Pennsylvania 19111.
Patricia
P
Kropf
D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001374:Azacitidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D000073399:DNA Demethylation; D000077209:Decitabine; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D059016:Tumor Microenvironment / Q000187:drug effects
D000964:Antimetabolites, Antineoplastic; D000077209:Decitabine; D001374:Azacitidine