Antisense therapy in oncology: new hope for an old idea?

Lancet. 2001 Aug 11;358(9280):489-97. doi: 10.1016/S0140-6736(01)05629-X.


There is a potential role for antisense oligonucleotides in the treatment of disease. The principle of antisense technology is the sequence-specific binding of an antisense oligonucleotide to target mRNA, resulting in the prevention of gene translation. The specificity of hybridisation makes antisense treatment an attractive strategy to selectively modulate the expression of genes involved in the pathogenesis of diseases. One antisense drug has been approved for local treatment of cytomegalovirus-induced retinitis, and several antisense oligonucleotides are in clinical trials, including oligonucleotides that target the mRNA of BCL2, protein-kinase-C alpha, and RAF kinase. Antisense oligonucleotides are well tolerated and might have therapeutic activity. Here, we summarise treatment ideas in this field, summarise clinical trials that are being done, discuss the potential contribution of CpG motif-mediated effects, and look at promising molecular targets to treat human cancer with antisense oligonucleotides.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Clinical Trials as Topic
  • Drug Design
  • Humans
  • In Vitro Techniques
  • Isoenzymes / metabolism
  • Neoplasms / drug therapy
  • Oligodeoxyribonucleotides, Antisense / therapeutic use
  • Oligonucleotides / therapeutic use
  • Oligonucleotides, Antisense / metabolism
  • Oligonucleotides, Antisense / therapeutic use*
  • Phosphorothioate Oligonucleotides
  • Protein Kinase C / metabolism
  • Protein Kinase C-alpha
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • RNA, Messenger / metabolism
  • Thionucleotides / therapeutic use


  • Antineoplastic Agents
  • GEM231
  • ISIS 2503
  • Isoenzymes
  • Oligodeoxyribonucleotides, Antisense
  • Oligonucleotides
  • Oligonucleotides, Antisense
  • Phosphorothioate Oligonucleotides
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • Thionucleotides
  • ISIS 3521
  • ISIS 5132
  • oblimersen
  • PRKCA protein, human
  • Protein Kinase C
  • Protein Kinase C-alpha