Prospects for prevention and treatment of cancer with selective PPARgamma modulators (SPARMs).
Peroxisome proliferator-activated receptor gamma (PPARgamma), 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 PPARgamma can be a significant risk factor for carcinogenesis, although in some cases overexpression enhances carcinogenesis. Ligands for PPARgamma 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 PPARgamma 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.
Sporn
M B
MB
Dept of Pharmacology, Dartmouth Medical School, Hanover, NH 03755, USA. michael.sporn@dartmouth.edu
Suh
N
N
Mangelsdorf
D J
DJ
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D004198:Disease Susceptibility; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control*; D011487:Protein Conformation; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000627:therapeutic use; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use; D014157:Transcription Factors / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D020845:Selective Estrogen Receptor Modulators; D014157:Transcription Factors