Peroxisomal proliferator-activated receptors (PPARs) are involved in the pathogenesis of insulin resistance, diabetes, and related complications. Consequently, the identification of PPAR subtypes and the potential for their activation provides promising therapeutic targets for the management of type 2 diabetes mellitus. Available data from rodent carcinogenicity studies, however, demonstrate that PPAR agonists can be tumorigenic in one or more species of rodents at multiple sites. The most commonly observed tumor types are hemangiosarcomas, fibro- and liposarcomas, and, in some cases, urinary bladder tumors. Mechanistic data are not yet available to explain the mode(s) of action for most of these tumor types. Outstanding questions exist regarding potency, species differences, safety margins, and other issues.
MISSION
The mission of the HESI PPAR Agonist Project Committee is to develop an improved scientific understanding of the human relevance of emerging rodent tumor data for PPAR agonists which hold promise in drug research and development. Participating scientists from international regulatory agencies, academia, and the pharmaceutical industry will develop consensus on the implications and long-term effects of PPAR agonist exposure by examining and integrating available pre-clinical data and evaluating the need for additional laboratory research.
For more information on the PPAR Agonist Project Committee’s membership and activities, click here.
To download an English version of the PPAR Agonist Fact Sheet, click here.