Antisense oligonucleotides show activity against Ras-mediated cancers

Antisense oligonucleotides (ODNs) that inhibit the kinase suppressor of ras-1 (KSR1) gene can prevent the growth of Ras-dependent malignancies, especially pancreatic cancer, new research shows.

In a study reported in the September 7th online issue of Nature Medicine, Dr. Richard Kolesnick and colleagues, from Memorial Sloan-Kettering Cancer Center in New York, tested the anti-cancer effects of ODNs in culture and in animal models of Ras-dependent pancreatic cancer and non-small-cell lung cancer.The authors found that the ODNs prevented the growth of pancreatic and lung cancer xenografts in nude mice. Further testing showed that such treatment caused the regression of established pancreatic tumors and inhibited lung metastases.No toxic effects were seen with any of the ODN doses used and this was confirmed on histologic analysis, the investigators point out.”KSR1 antisense ODNs might be used to treat human pancreatic cancer, which presently lacks effective therapeutic regimens,” the researchers state. “To explore this possibility, a phase I clinical trial for KSR1 inactivation in human pancreatic cancer is being planned at Memorial Sloan-Kettering Cancer Center,” they add.(Source: Nat Med, online 7 September 2003: Reuters Health: September 8, 2003: Oncolink)