Combinatorial chemoprevention of intestinal neoplasia.

Abstract

A combination of two drugs afforded remarkable protection from intestinal neoplasia in APC(Min/+) mice, a murine model of human familial adenomatous polyposis (FAP). One of the drugs was sulindac, a prototypical non-steroidal anti-inflammatory drug with established chemopreventative activity. The second drug was EKI-569, a newly developed, irreversible inhibitor of the epidermal growth factor receptor kinase. Although 100% of the untreated APC(Min/+) mice developed approximately 20 polyps, nearly half the mice treated with these two agents developed no polyps at all. These results suggest a powerful strategy for the chemoprevention of human colonic neoplasia.

• Authors: C J Torrance, P E Jackson, E Montgomery, K W Kinzler, B Vogelstein, A Wissner, M Nunes, P Frost, C M Discafani
• Journal: Nature medicine (Nat Med) Vol. 6 Issue 9 Pg. 1024-8 (Sep 2000) ISSN: 1078-8956 [Print] United States
• PMID: 10973323 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Aminoquinolines
• Aniline Compounds
• Anti-Inflammatory Agents, Non-Steroidal
• Antineoplastic Agents
• Enzyme Inhibitors
• Organic Chemicals
• Quinazolines
• Sulindac
• CL 387785
• ErbB Receptors
• EKB 569

Topics

• Adenomatous Polyposis Coli (prevention & control)
• Aminoquinolines
• Aniline Compounds
• Animals
• Anti-Inflammatory Agents, Non-Steroidal (therapeutic use)
• Antineoplastic Agents (therapeutic use)
• Drug Therapy, Combination
• Enzyme Inhibitors (therapeutic use)
• ErbB Receptors (antagonists & inhibitors)
• Mice
• Mice, Mutant Strains
• Organic Chemicals
• Quinazolines (therapeutic use)
• Sulindac (therapeutic use)