PPAR Research (Jan 2008)
PPARš¾ and Agonists against Cancer: Rational Design of Complementation Treatments
Abstract
PPARš¾ is a member of the ligand-activated nuclear receptor superfamily: its ligands act as insulin sensitizers and some are approved for the treatment of metabolic disorders in humans. PPARš¾ has pleiotropic effects on survival and proliferation of multiple cell types, including cancer cells, and is now subject of intensive preclinical cancer research. Studies of the recent decade highlighted PPARš¾ role as a potential modulator of angiogenesis in vitro and in vivo. These observations provide an additional facet to the PPARš¾ image as potential anticancer drug. Currently PPARš¾ is regarded as an important target for the therapies against angiogenesis-dependent pathological states including cancer and vascular complications of diabetes. Some of the studies, however, identify pro-angiogenic and tumor-promoting effects of PPARš¾ and its ligands pointing out the need for further studies. Below, we summarize current knowledge of PPARš¾ regulatory mechanisms and molecular targets, and discuss ways to maximize the beneficial activity of the PPARš¾ agonists.