PPARγ and agonists against cancer: Rational design of complementation treatments

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