RAF antisense oligonucleotide as a tumor radiosensitizer

Oncogene. 2003 Sep 1;22(37):5876-84. doi: 10.1038/sj.onc.1206700.


The RAF-1 serine-threonine kinase plays a central role in signal transduction pathways involved in cell survival and proliferation. The concept of RAF-1-targeted disruption of cell signaling for therapeutic purposes was first advanced in 1989 with the demonstration of tumor growth inhibition in athymic mice and radiosensitization of human squamous carcinoma cells transfected with a vector expressing antisense cDNA. However, the clinical application of antisense strategies has awaited the development of improved antisense oligonucleotide technologies and drug delivery methods. Nuclease-resistant phosphorothioated antisense oligonucleotides have been the focus of pharmaceutical industry attention. In vivo delivery of nuclease-sensitive, natural backbone/phosphodiester oligonucleotides has remained a formidable challenge. Liposomal encapsulation of antisense oligonucleotides protects them from degradation and enhances drug delivery. Here, we review the importance of targeting RAF-1 signaling in cancer therapy and the preclinical and clinical experiences with a liposomal formulation of a nuclease-sensitive, ends-modified antisense RAF oligonucleotide.

Publication types

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

MeSH terms

  • Animals
  • Humans
  • Neoplasms / radiotherapy*
  • Oligonucleotides, Antisense / pharmacology*
  • Proto-Oncogene Proteins c-raf / radiation effects*


  • Oligonucleotides, Antisense
  • Proto-Oncogene Proteins c-raf