Pharmacologic inactivation of kinase suppressor of ras-1 abrogates Ras-mediated pancreatic cancer

Nat Med. 2003 Oct;9(10):1266-8. doi: 10.1038/nm927. Epub 2003 Sep 7.

Abstract

Inhibition of the kinase suppressor of ras-1 (KSR1) gene by continuous infusion of phosphorothioate antisense oligonucleotides (ODNs) prevented growth of K-Ras-dependent human PANC-1 pancreatic and A549 non-small-cell lung carcinoma xenografts in nude mice, effected regression of established PANC-1 tumors and inhibited A549 lung metastases, all without apparent toxicity. These studies suggest KSR1 antisense ODNs as a treatment for Ras-dependent human malignancies, in particular pancreatic cancer, which lacks effective curative therapy.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Genes, ras*
  • Humans
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Oligonucleotides, Antisense / metabolism
  • Oligonucleotides, Antisense / therapeutic use*
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • Protein Kinases / genetics*
  • Protein Kinases / metabolism
  • Transplantation, Heterologous

Substances

  • Oligonucleotides, Antisense
  • Protein Kinases
  • KSR-1 protein kinase