title: Telomeres as targets for anticancer therapies.
abstract: BACKGROUND
  The limitless replicative potential of cancer cells relies on telomere integrity (which is guaranteed by a complex interaction between several specialized proteins and telomeric DNA) and the activation of specific mechanisms for telomere length maintenance. Two mechanisms are currently known in human cancer, namely telomerase activity and the alternative lengthening of telomere pathway.
  
  
  CONCLUSIONS
  In this review, we summarize the available data concerning the therapeutic strategies proposed thus far and the current challenges posed for the development of innovative telomere-based therapeutic approaches with broad-spectrum anticancer activity and for their translation into the clinical setting.
  
  
  METHODS
  Due to their essential role in tumor cell proliferation, telomere maintenance mechanisms have become extremely attractive targets for the development of new anticancer interventions. Although numerous efforts have been made to identify specific approaches to interfere with telomere maintenance mechanisms in human cancers, the only molecule currently tested in clinical trials is the oligonucleotide GRN163L. However, a growing body of evidence suggests that interfering with telomeres, through the direct targeting of telomeric G-quadruplex structures, may be a valuable antitumor therapeutic strategy, independent of the specific telomere maintenance mechanism operating in the tumor.
authors.affiliation: Fondazione IRCCS Istituto Nazionale Tumori, Department of Experimental Oncology and Molecular Medicine, Milan, Italy. marco.folini@istitutotumori.mi.it
authors.forename: Marco
authors.initials: M
authors.lastname: Folini
authors.forename: Lorenza
authors.initials: L
authors.lastname: Venturini
authors.forename: Graziella
authors.initials: G
authors.lastname: Cimino-Reale
authors.forename: Nadia
authors.initials: N
authors.lastname: Zaffaroni
mesh_terms: D000818:Animals; D054856:G-Quadruplexes / Q000187:drug effects; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D019098:Telomerase / Q000037:antagonists & inhibitors; D016615:Telomere / Q000187:drug effects* / Q000502:physiology; D035341:Telomeric Repeat Binding Protein 2 / Q000037:antagonists & inhibitors
chemical_list: D035341:Telomeric Repeat Binding Protein 2; D019098:Telomerase