The Role of PPARγ Ligands in Breast Cancer: From Basic Research to Clinical Studies.

Abstract

Simple SummaryBreast cancer represents the most frequently diagnosed carcinoma and the leading cause of cancer death in women. Despite advances achieved in systemic therapy, about one-third of all patients relapse and develop a metastatic disease, which ultimately leads to breast cancer deaths. In this scenario, the identification of new prognostic factors and pharmacological tools is needed to improve breast cancer management. Peroxisome proliferator-activated receptor gamma (PPARγ), belonging to the nuclear receptor superfamily, is a ligand-dependent transcription factor expressed in many tumors including breast cancer, and its function upon binding of ligands has been linked to the tumor development, progression and metastasis. Over the last decade, much research has focused on the implication of natural and synthetic PPARγ agonists in the negative regulation of breast cancer growth and progression. The aim of the present review is to summarize the role of PPARγ activation in breast cancer from the basic research to clinical studies. The therapeutic effects of natural and synthetic PPARγ ligands, as antineoplastic agents, represent a fascinating and clinically a potential translatable area of research with regards to the battle against cancer.Peroxisome proliferator-activated receptor gamma (PPARγ), belonging to the nuclear receptor superfamily, is a ligand-dependent transcription factor involved in a variety of pathophysiological conditions such as inflammation, metabolic disorders, cardiovascular disease, and cancers. In this latter context, PPARγ is expressed in many tumors including breast cancer, and its function upon binding of ligands has been linked to the tumor development, progression, and metastasis. Over the last decade, much research has focused on the potential of natural agonists for PPARγ including fatty acids and prostanoids that act as weak ligands compared to the strong and synthetic PPARγ agonists such as thiazolidinedione drugs. Both natural and synthetic compounds have been implicated in the negative regulation of breast cancer growth and progression. The aim of the present review is to summarize the role of PPARγ activation in breast cancer focusing on the underlying cellular and molecular mechanisms involved in the regulation of cell proliferation, cell cycle, and cell death, in the modulation of motility and invasion as well as in the cross-talk with other different signaling pathways. Besides, we also provide an overview of the in vivo breast cancer models and clinical studies. The therapeutic effects of natural and synthetic PPARγ ligands, as antineoplastic agents, represent a fascinating and clinically a potential translatable area of research with regards to the battle against cancer.