title: Antisense oligonucleotides in cancer.
abstract: OBJECTIVE
  Over the past several dozen years, regardless of the substantial effort directed toward developing rational oligonucleotide strategies to silence gene expression, antisense oligonucleotide-based cancer therapy has not been successful. This review focuses on the most likely reasons for this lack of success, and on the barriers that still need to be overcome to make a clinical cancer treatment reality out of the promise of antisense therapy.
  
  
  RESULTS
  Considerable progress has been made in the design and delivery of nucleic acid fragments. Chemical modifications have considerably improved oligonucleotide absorption, distribution and metabolism while at the same time reducing toxicity. Nevertheless, the delivery and the cellular uptake of these molecules are still not adequate to provide the desired therapeutic outcome. Recent therapeutic interventional phase III trials of antisense oligodeoxyribonucleotides for a cancer indication will be discussed, in addition to those studies that markedly improve the scientific understanding of the properties of these molecules.
  
  
  CONCLUSIONS
  We still do not have a marketed antisense oligonucleotide for a cancer indication. This is because critical aspects of the cellular, tumor pharmacology and delivery properties of these agents are still not well understood.
authors.affiliation: Department of Medical Oncology and Experimental Therapeutics, City of Hope, Duarte, California, USA.
authors.forename: Daniela
authors.initials: D
authors.lastname: Castanotto
authors.forename: Cy A
authors.initials: CA
authors.lastname: Stein
mesh_terms: D000818:Animals; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D009369:Neoplasms / Q000628:therapy*; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use*
chemical_list: D016376:Oligonucleotides, Antisense