Prospects for prevention and treatment of cancer with selective PPAR gammamodulators (SPARMs)

Peroxisome proliferator-activated receptor gamma (PPAR gamma), a nuclear re ceptor 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 PPAR gamma can be a significant risk factor for carcinogenesis, although in some cases overexpression enhances carcinogenesis. Ligands for PPAR gam ma suppress breast carcinogenesis in experimental models and induce differe ntiation of human liposarcoma cells. By analogy to the selective estrogen r eceptor modulator (SERM) concept, it is suggested that selective PPAR gamma modulators (SPARMs), designed to have desired effects on specific genes an d target tissues without undesirable effects on others, will be clinically important in the future for chemoprevention and chemotherapy of cancer.