The emerging role of PPAR-alpha in breast cancer

Breast cancer has been confirmed to have lipid disorders in the tumour microenvironment. Peroxisome proliferator-activated receptor alpha (PPAR alpha) is a ligand-activated transcriptional factor that belongs to the family of nuclear receptors. PPAR alpha regulates the expression of genes involved in fatty acid homeostasis and is a major regulator of lipid metabolism. Because of its effects on lipid metabolism, an increasing number of studies have investigated the relationship of PPAR alpha with breast cancer. PPAR alpha has been shown to impact the cell cycle and apoptosis in normal cells and tumoral cells through regulating genes of the lipogenic pathway, fatty acid oxidation, fatty acid activation, and uptake of exogenous fatty acids. Besides, PPAR alpha is involved in the regulation of the tumour microenvironment (anti-inflammation and inhibition of angiogenesis) by modulating different signal pathways such as NF-kappa B and PI3K/AKT/mTOR. Some synthetic PPAR alpha ligands are used in adjuvant therapy for breast cancer. PPAR alpha agonists are reported to reduce the side effects of chemotherapy and endocrine therapy. In addition, PPAR alpha agonists enhance the curative effects of targeted therapy and radiation therapy. Interestingly, with the emerging role of immunotherapy, attention has been focused on the tumour microenvi-ronment. The dual functions of PPAR alpha agonists in immunotherapy need further research. This review aims to consolidate the operations of PPAR alpha in lipid-related and other ways, as well as discuss the current and potential applications of PPAR alpha agonists in tackling breast cancer.

Automated summary

Breast cancer is associated with lipid disorders and PPAR alpha has been found to regulate various processes in cancer cells, including cell cycle and apoptosis, and the tumor microenvironment. PPAR alpha agonists are used as adjuvant therapy for breast cancer, reducing side effects of chemotherapy and enhancing the efficacy of targeted therapy and radiation therapy. However, further research is needed on the role of PPAR alpha agonists in immunotherapy.