A Role for the PPARγin Cancer Therapy

Abstract

In 1997, the first published reports highlighted PPARγas a novel cancer therapeutic target regulating differentiation of cancer cells. A subsequent flurry of papers described these activities more widely and fuelled further enthusiasm for differentiation therapy, as the ligands for the PPARγwere seen as well tolerated and in several cases well-established in other therapeutic contexts. This initial enthusiasm and promise was somewhat tempered by contradictory findings in several murine cancer models and equivocal trial findings. As more understanding has emerged in recent years, a renaissance has occurred in targeting PPARγwithin the context of either chemoprevention or chemotherapy. This clarity has arisen in part through a clearer understanding of PPARγbiology, how the receptor interacts with other proteins and signaling events, and the mechanisms that modulate its transcriptional actions. Equally greater translational understanding of this target has arisen from a clearer understanding of in vivo murine cancer models. Clinical exploitation will most likely require precise and quantifiable description of PPARγactions, and resolution of which targets are the most beneficial to target combined with an understanding of the mechanisms that limits its anticancer effectiveness.