Prospects for prevention and treatment of cancer with selective PPARγ modulators (SPARMs)

Peroxisome proliferator-activated receptor γ (PPARγ), a nuclear receptor and transcription factor that regulates the expression of many genes relevant to carcinogenesis, is now an important target for development of new drugs for the prevention and treatment of cancer. Deficient expression of PPARγ can be a significant risk factor for carcinogenesis, although in some cases overexpression enhances carcinogenesis. Ligands for PPARγ suppress breast carcinogenesis in experimental models and induce differentiation of human liposarcoma cells. By analogy to the selective estrogen receptor modulator (SERM) concept, it is suggested that selective PPARγ modulators (SPARMs), designed to have desired effects on specific genes and target tissues without undesirable effects on others, will be clinically important in the future for chemoprevention and chemotherapy of cancer.