title: Epigenetic control of gene expression: Potential implications for cancer treatment.
abstract: Epigenetic changes are defined as inherited modifications that are not present in DNA sequence. Gene expression is regulated at various levels and not only in response to DNA modifications. Examples of epigenetic control are DNA methylation, histone deacetylation and mi-RNA expression. Methylation of several tumor suppressor gene promoters is responsible for their silencing and thus potentially sustain cancerogenesis. Similarly, histone deacetylation can lead to oncogene activation. mi-RNA are small (18-20 nucleotides) non-coding RNA fragments capable of inhibiting other m-RNA, ultimately altering the balance in oncogene and tumor suppressor gene expression. It has been shown that growth of several tumor types can be stimulated by epigenetic changes in various phases of cancerogenesis, and drugs able to interfere with these mechanisms can have a positive impact on tumor progression. As matter of fact, epigenetic changes are dynamic and can be reversed by epigenetic inhibitors. Recently, methyltransferase and histone deacetylase inhibitors have attracted the attention of researchers and clinicians as they potentially provide alternative therapeutic options in some cancers. Drugs that inhibit DNA methylation or histone deacetylation have been studied for the reactivation of tumor suppressor genes and repression of cancer cell growth. Epigenetic inhibitors work alone or in combination with other therapeutic agents. To date, a number of epigenetic inhibitors have been approved for cancer treatment. The main challenge in the field of epigenetic inhibitors is their lack of specificity. In this review article we describe their mechanisms of action and potential in cancer treatment.
authors.affiliation: Medical Oncology Unit, POC SS Annunziata, Taranto, Italy. Electronic address: francesco.perri80@alice.it.
authors.forename: F
authors.initials: F
authors.lastname: Perri
authors.affiliation: Otolaryngology Unit, National Tumor Institute of Naples, G. Pascale, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Longo
authors.affiliation: Department of Clinical Medicine and Surgery, University of Naples 'Federico II', Napoli, Italy; dLester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA.
authors.forename: M
authors.initials: M
authors.lastname: Giuliano
authors.affiliation: Medical Oncology Department, University of Salerno, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Sabbatino
authors.affiliation: Otolaryngology Unit, University of Bari, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Favia
authors.affiliation: Otolaryngology Unit, National Tumor Institute of Naples, G. Pascale, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Ionna
authors.affiliation: San Giovanni di Dio Hospital, Department of Medical Oncology, Frattamaggiore, Naples, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Addeo
authors.affiliation: Medical Oncology Unit, POC SS Annunziata, Taranto, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Della Vittoria Scarpati
authors.affiliation: Medical Oncology Unit, University of Naples "Federico II", Italy.
authors.forename: G
authors.initials: G
authors.lastname: Di Lorenzo
authors.affiliation: Medical Oncology Unit, POC SS Annunziata, Taranto, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Pisconti
mesh_terms: D063646:Carcinogenesis / Q000235:genetics; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D015870:Gene Expression; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D011401:Promoter Regions, Genetic
chemical_list: D056572:Histone Deacetylase Inhibitors
keywords: Cancer; Epigenetics; Oncogenes; Therapy; Tumor suppressor genes