PPARα antagonists as cytotoxic agents in gliomas and pancreatic, colorectal, and renal cancer

Peroxisome Proliferator-Activated Receptors (PPARs) are proteins belonging to the nuclear receptor superfamily, expressed in metabolically active tissues. Three receptor subtypes have been identified, designated as PPARα, PPARδ and PPARγ, which contribute, each with its peculiarities and functions, to the regulation of lipid and glucose homeostasis. In recent years, the involvement of PPARs in the development of tumors has become increasingly evident, although the exact role of this isoform is still controversial.

An increased PPARα activation has been found to result progression and growth in many cancers, including leukemia, prostate, ovarian, and renal cell carcinomas, where a metabolic switch from glucose to fatty acid oxidation (FAO) occurs. In this context, the PPARα antagonists showed cytotoxic activity in different cancer cell lines expressing PPARα, as chronic lymphocytic leukemia and renal cell carcinoma.

In this presentation the effects of some PPARα antagonists with sulfonimide structure on gliomas and pancreatic, colorectal, and renal cancer will be illustrated.