PPARγ and Agonists against Cancer: Rational Design of Complementation Treatments

PPAR γ 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. PPAR γ 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 PPAR γ role as a potential modulator of angiogenesis in vitro and in vivo. These observations provide an additional facet to the PPAR γ image as potential anticancer drug. Currently PPAR γ 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 PPAR γ and its ligands pointing out the need for further studies. Below, we summarize current knowledge of PPAR γ regulatory mechanisms and molecular targets, and discuss ways to maximize the beneficial activity of the PPAR γ agonists.