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

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.

• Authors: H Rosie Xing, Carlos Cordon-Cardo, Xinzhu Deng, William Tong, Luis Campodonico, Zvi Fuks, Richard Kolesnick
• Journal: Nature medicine (Nat Med) Vol. 9 Issue 10 Pg. 1266-8 (Oct 2003) ISSN: 1078-8956 [Print] United States
• PMID: 12960962 (Publication Type: Journal Article)

Chemical References

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

Topics

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