title: Poly(ADP-Ribose) Polymerases: New Players in the Pathogenesis of Exocrine Pancreatic Diseases.
abstract: The poly(ADP-ribose) polymerase (PARP) enzymes were initially characterized as sensors of DNA breaks but are now known to play key roles not only in the DNA damage response but also in regulating numerous molecular processes, such as gene transcription. Furthermore, these polymerases have emerged as key players in the pathogenesis of multiple diseases, providing promising therapeutic targets for pathologies such as cardiovascular disorders, neurodegenerative diseases, and cancer. In recent years, PARPs have been implicated in the pathogenesis of pancreatitis and pancreatic cancer, and PARP inhibition has been proposed as a valuable strategy for treating these two important gastrointestinal tract disorders. For instance, in preclinical mouse models, pancreatitis was significantly attenuated after genetic or pharmacological PARP inactivation, and several clinical trials have demonstrated promising responses to PARP inhibitors in pancreatic cancer patients. In this review, we summarize the current understanding of PARP functions in these two dismal pathologies and discuss the next steps necessary to determine whether PARP inhibitors will finally make the difference in treating pancreatitis and pancreatic cancer successfully.
authors.affiliation: Cancer Research Program, IMIM-Hospital del Mar Medical Research Institute, Barcelona, Spain.
authors.forename: Neus
authors.initials: N
authors.lastname: Martínez-Bosch
authors.affiliation: Division of Oncology Research, Schulze Center for Novel Therapeutics, Mayo Clinic, Rochester, Minnesota.
authors.forename: Martin E
authors.initials: ME
authors.lastname: Fernández-Zapico
authors.affiliation: Cancer Research Program, IMIM-Hospital del Mar Medical Research Institute, Barcelona, Spain. Electronic address: pnavarro@imim.es.
authors.forename: Pilar
authors.initials: P
authors.lastname: Navarro
authors.affiliation: Cancer Research Program, IMIM-Hospital del Mar Medical Research Institute, Barcelona, Spain; Network Center for Biomedical Research on Hepatic and Digestive Diseases, Madrid, Spain; Department of Immunology, Hospital del Mar, Barcelona, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Yélamos
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D010182:Pancreatic Diseases / Q000188:drug therapy / Q000378:metabolism; D000067856:Poly(ADP-ribose) Polymerase Inhibitors / Q000494:pharmacology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*
chemical_list: D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases