Establishing the Role of PPARβ/δ in Carcinogenesis

The role of the nuclear hormone receptor peroxisome proliferator-activated receptor β/δ (PPARβ/δ) in carcinogenesis is controversial because conflicting studies indicate that it both inhibits and promotes tumorigenesis. In this review, we focus on recent studies on PPARβ/δ including the significance of increased or decreased PPARβ/δ expression in cancers; a range of opposing mechanisms describing how PPARβ/δ agonists, antagonists, and inverse agonists regulate tumorigenesis and/or whether there may be cell context-specific mechanisms; and whether activating or inhibiting PPARβ/δ is feasible for cancer chemoprevention and/or therapy. Research questions that need to be addressed are highlighted to establish whether PPARβ/δ can be effectively targeted for cancer chemoprevention.

TrendsPPARβ/δ expression in cancers requires careful quantification and validation.Given that PPARβ/δ is constitutively high expressed and regulates multiple pathways involved in carcinogenesis, and natural and synthetic agonists, antagonists, and inverse agonists already exist, it has great potential as a target for cancer chemoprevention.Dissecting the role of PPARβ/δ in tumor and host cells in the tumor microenvironment, including in patients with cancer where PPARβ/δ expression correlates with clinical outcomes, is warranted.Analyzing the role of PPARβ/δ in tumorigenesis in human models and different strains of Ppard transgenic mice will help exclude potential contributions by modifier genes.Collaborations between laboratories describing opposing effects of PPARβ/δ in cancer could have a major positive impact in this field.