title: Targeting the microRNA-regulating DNA damage/repair pathways in cancer.
abstract: BACKGROUND
  Maintenance of genome stability requires the integrity of the DNA repair machinery. DNA damage response (DDR) determines cell fate and regulates the expression of microRNAs (miRNAs), which in turn may also regulate important components of the DNA repair machinery.
  
  
  METHODS
  In this review, we describe the bidirectional connection between miRNAs and DDR and their link with important biological functions such as, DNA repair, cell cycle and apoptosis in cancer. Furthermore, we highlight the potential implications of recent findings on miRNA/DDR in determining chemotherapy response in cancer patients, and the use of these biomarkers for novel potential therapeutic approaches.
  
  
  CONCLUSIONS
  Defects in the DDR and deregulation of miRNAs are important hallmarks of human cancer. A full understanding of the mechanisms underlying the connection between miRNAs and DDR/DNA repair pathways will positively impact our knowledge on human tumor biology and on different responses to distinct drugs. Specific miRNAs interact with distinct DDR components and are promising targets for enhancing the effects of, and/or to overcome the resistance to, conventional chemotherapeutic agents. Finally, the development of innovative tools to deliver miRNA-targeting oligonucleotides may represents novel types of cancer interventions in clinic.
authors.affiliation: IRCCS Clinical and Research Institute Humanitas, Experimental Therapeutics Unit , Via Manzoni 113 - 20089 Rozzano, Milan , Italy +39 02 8224 5173 ; +39 02 8224 5191 ; libero.santarpia@humanitasresearch.it ; liberosantarpia@yahoo.it.
authors.forename: Giulia
authors.initials: G
authors.lastname: Bottai
authors.forename: Barbara
authors.initials: B
authors.lastname: Pasculli
authors.forename: George A
authors.initials: GA
authors.lastname: Calin
authors.forename: Libero
authors.initials: L
authors.lastname: Santarpia
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D004249:DNA Damage / Q000187:drug effects / Q000502:physiology*; D004260:DNA Repair / Q000187:drug effects / Q000502:physiology*; D016503:Drug Delivery Systems / Q000639:trends*; D018390:Gene Targeting / Q000639:trends*; D042822:Genomic Instability / Q000502:physiology; D006801:Humans; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000502:physiology*; D009369:Neoplasms / Q000235:genetics* / Q000628:therapy*
chemical_list: D000970:Antineoplastic Agents; D035683:MicroRNAs
keywords: DNA damage response; DNA repair; apoptosis; cancer therapies; cell cycle; chemotherapy; drug response; microRNAs