title: G-quadruplexes: targets and tools in anticancer drug design.
abstract: BACKGROUND
  Guanosine (G)-rich DNA and RNA sequences can adopt a defined secondary structure, the G-quadruplex, which consists of multiple stacked G-tetrads. Each G-tetrad has four Gs arranged in a planar configuration and held together by hydrogen bonding. G-quadruplexes are found in chromosomal DNA and RNA transcripts, particularly in telomeric sequences, and in regulatory regions of many genes including oncogenes.
  
  
  OBJECTIVE
  This review summarizes how G-quadruplexes can be employed for anticancer therapies and discusses possible mechanisms.
  
  
  METHODS
  The Medline database was searched using the terms "G-rich oligonucleotide (GRO)", "G-tetrad", and "G-quadruplex".
  
  
  RESULTS
  Drugs which bind to and stabilize G-quadruplexes can be employed to suppress the elongation of telomers and the gene transcription and translation of oncogenes. G-quadruplex stabilization results in senescence and apoptosis of cancer cells. Besides long-chain nucleic acids, also GRO are able to acquire G-quadruplex conformation to build up a variety of stable structures. Selected aptamers show a highly specific binding capacity to their target molecules, similar to antibodies. Some GRO were shown to induce cell death, preferentially in cancer cells; they demonstrated remarkable anticancer activity in preclinical and first clinical studies.
  
  
  CONCLUSIONS
  G-quadruplexes can be both, targets and tools in anticancer drug development.
authors.affiliation: Department of Bioorganic Chemistry, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Łódź, Poland. mduchler@cbmm.lodz.pl
authors.forename: Markus
authors.initials: M
authors.lastname: Düchler
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015195:Drug Design; D054856:G-Quadruplexes; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009857:Oncogenes / Q000235:genetics; D016615:Telomere / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents