Pharmacologic inactivation of kinase suppressor of ras-1 abrogates Ras-mediated pancreatic cancer.
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.
Xing
H Rosie
HR
Laboratory of Signal Transduction, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA.
Cordon-Cardo
Carlos
C
Deng
Xinzhu
X
Tong
William
W
Campodonico
Luis
L
Fuks
Zvi
Z
Kolesnick
Richard
R
D000818:Animals; D045744:Cell Line, Tumor; D011905:Genes, ras; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D016376:Oligonucleotides, Antisense / Q000378:metabolism / Q000627:therapeutic use*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism; D014183:Transplantation, Heterologous
D016376:Oligonucleotides, Antisense; D011494:Protein Kinases; C097199:KSR-1 protein kinase