First author Rajnish Gupta and colleagues administered the PPARδ agonist GW501516 to mice lacking the adenomatous polyposis coli (APC) tumor suppressor; these animals have a high risk for colorectal cancers. The drug led to a significant increase in both the size and number of intestinal polyps. Control mice had, on average, 28 small-intestine polyps, whereas drug-treated animals had twice as many. When the authors counted polyps over 2 mm in diameter, however, they found a 10-fold greater incidence in the treated animals, suggesting that the agonist lead to an increase in polyp size.

While the authors caution that PPARδ agonists should be evaluated fully for proneoplastic effects before they are used in the clinic, there is no indication that activation of PPARγ pathways play a role in polyp growth. In fact, the authors explicitly state that GW501516 is a subtype-selective agonist for the PPAR family, binding only to the δ isoform.—Tom Fagan.

Reference:
Gupta RA, Wang D, Katkuri S, Wang H, Dey SK, DuBois RN. Activation of nuclear hormone receptor peroxisome proliferator-activated receptor-delta accelerates intestinal adenoma growth. Nat Med. 2004 Feb 1 [Epub ahead of print] Abstract