Combinatorial Chemoprevention of Intestinal Neoplasia

Nat Med. 2000 Sep;6(9):1024-8. doi: 10.1038/79534.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 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*

Substances

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