title: Demethylation and re-expression of epigenetically silenced tumor suppressor genes: sensitization of cancer cells by combination therapy.
abstract: Epigenetic regulation in eukaryotic and mammalian systems is a complex and emerging field of study. While histone modifications create an open chromatin conformation allowing for gene transcription, CpG methylation adds a further dimension to the expression of specific genes in developmental pathways and carcinogenesis. In this review, we will highlight DNA methylation as one of the distinct mechanisms for gene silencing and try to provide insight into the role of epigenetics in cancer progenitor cell formation and carcinogenesis. We will also introduce the concept of a dynamic methylation-demethylation system and the potential for the existence of a demethylating enzyme in this process. Finally, we will explain how re-expression of epigenetically silenced tumor suppressor genes could be exploited to develop effective drug therapies. In particular, we will consider how a combination therapy that includes epigenetic drugs could possibly kill cancer progenitor cells and reduce the chance of relapse following chemotherapy.
authors: Cancer Center, Boston University School of Medicine, Boston, MA 02118, USA. ss1@bu.edu
authors: Sibaji
authors: S
authors: Sarkar
authors: Sarah
authors: S
authors: Goldgar
authors: Shannon
authors: S
authors: Byler
authors: Shoshana
authors: S
authors: Rosenthal
authors: Sarah
authors: S
authors: Heerboth
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D019175:DNA Methylation / Q000187:drug effects / Q000235:genetics*; D004151:Dipeptides / Q000008:administration & dosage; D044127:Epigenesis, Genetic / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D016147:Genes, Tumor Suppressor / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
chemical_list: D004151:Dipeptides; D056572:Histone Deacetylase Inhibitors; C071482:calpeptin