Combinatorial chemoprevention of intestinal neoplasia.
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.
Torrance
C J
CJ
The Howard Hughes Medical Institute and The Johns Hopkins Oncology Center, Baltimore, Maryland 21231, USA.
Jackson
P E
PE
Montgomery
E
E
Kinzler
K W
KW
Vogelstein
B
B
Wissner
A
A
Nunes
M
M
Frost
P
P
Discafani
C M
CM
D011125:Adenomatous Polyposis Coli / Q000517:prevention & control*; D000634:Aminoquinolines; D000814:Aniline Compounds; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D051379:Mice; D008817:Mice, Mutant Strains; D009930:Organic Chemicals; D011799:Quinazolines / Q000627:therapeutic use; D013467:Sulindac / Q000627:therapeutic use*
D000634:Aminoquinolines; D000814:Aniline Compounds; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D009930:Organic Chemicals; D011799:Quinazolines; D013467:Sulindac; C118029:CL 387785; D066246:ErbB Receptors; C413879:EKB 569