title: Histone Deacetylase (HDAC) Inhibitors: Current Evidence for Therapeutic Activities in Pancreatic Cancer.
abstract: Pancreatic carcinoma is one of the leading causes of cancer death. Current standard treatments include surgical resection, chemotherapy and radiotherapy but patient's prognosis remains poor and present severe side-effects. Contemporary oncology found a wide variety of novel anticancer drugs that regulate the epigenetic mechanisms of tumor genesis. Histone deacetylases (HDACs) are enzymes with pleiotropic activities that control critical functions of the cell through regulation of the acetylation states of histone proteins and other non-histone protein targets. They are divided into four groups, each with different localization in the cell, role and structure. Histone deacetylase inhibitors (HDACIs) are substances, which inhibit the function of HDACs. We recognize four leading groups (hydroxamic acid, cyclic tetrapeptide, benzamide, aliphatic acid). There are many HDACIs currently in pre-clinical and two (vorinostat, romidepsin) in clinical stages of investigation for pancreatic cancer. Numerous studies argue for the use HDACIs as monotherapy, others suggest that combination of HDACIs with other antitumor drugs has better therapeutic results. This review focuses on the use of HDACIs as novel anticancer drugs and will explain the mechanisms of therapeutic effect on pancreatic cancer.
authors.affiliation: Second Department of Propedeutic Surgery, "Laiko" General Hospital, National and Kapodistrian University of Athens, Medical School, Athens, Greece x_damaskos@yahoo.gr.
authors.forename: Christos
authors.initials: C
authors.lastname: Damaskos
authors.affiliation: Second Department of Propedeutic Surgery, "Laiko" General Hospital, National and Kapodistrian University of Athens, Medical School, Athens, Greece x_damaskos@yahoo.gr.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Garmpis
authors.affiliation: Second Department of Propedeutic Surgery, "Laiko" General Hospital, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
authors.forename: Theodore
authors.initials: T
authors.lastname: Karatzas
authors.affiliation: Department of Internal Medicine, "Ygeias Melathron" Hospital, Athens, Greece.
authors.forename: Lampros
authors.initials: L
authors.lastname: Nikolidakis
authors.affiliation: Second Department of Propedeutic Surgery, "Laiko" General Hospital, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
authors.forename: Ioannis D
authors.initials: ID
authors.lastname: Kostakis
authors.affiliation: Second Department of Propedeutic Surgery, "Laiko" General Hospital, National and Kapodistrian University of Athens, Medical School, Athens, Greece x_damaskos@yahoo.gr.
authors.forename: Anna
authors.initials: A
authors.lastname: Garmpi
authors.affiliation: National and Kapodistrian University of Athens, Medical School, Athens, Greece.
authors.forename: Stefanos
authors.initials: S
authors.lastname: Karamaroudis
authors.affiliation: Department of Surgery, "Naval and Veterans" Hospital, Athens, Greece.
authors.forename: Georgios
authors.initials: G
authors.lastname: Boutsikos
authors.affiliation: Department of Internal Medicine, "Ygeias Melathron" Hospital, Athens, Greece.
authors.forename: Zoi
authors.initials: Z
authors.lastname: Damaskou
authors.affiliation: Biomedical Research Foundation (IIBEA), Academy of Athens, Athens, Greece.
authors.forename: Alkiviadis
authors.initials: A
authors.lastname: Kostakis
authors.affiliation: Second Department of Propedeutic Surgery, "Laiko" General Hospital, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
authors.forename: Gregory
authors.initials: G
authors.lastname: Kouraklis
mesh_terms: D001549:Benzamides / Q000627:therapeutic use; D063646:Carcinogenesis / Q000187:drug effects*; D044127:Epigenesis, Genetic / Q000187:drug effects*; D005227:Fatty Acids / Q000627:therapeutic use; D056572:Histone Deacetylase Inhibitors / Q000145:classification / Q000627:therapeutic use*; D006655:Histone Deacetylases / Q000187:drug effects; D006801:Humans; D006877:Hydroxamic Acids / Q000627:therapeutic use; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D001549:Benzamides; D005227:Fatty Acids; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C037689:benzamide; D006655:Histone Deacetylases
keywords: HDAC; acetylasation; epigenetics; histone; inhibitors; pancreatic cancer; review