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Clinical Cancer Research Vol. 9, 1-9, January 2003
© 2003 American Association for Cancer Research

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Peroxisome Proliferator-activated Receptor {gamma} and Cancers1

H. Phillip Koeffler2

Cedars-Sinai Medical Center/University of California, Los Angeles School of Medicine, Division of Hematology/Oncology, Los Angeles, California 90048

The peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) ligands have anticancer activity against a wide variety of neoplastic cells in vitro. Animal studies have chronicled their in vivo anticancer effects and chemopreventive capabilities. In addition, moderate anticancer activities of PPAR{gamma} ligands with minimal toxicities have been observed in patients with liposarcomas and prostate cancers. These compounds can slow growth and induce partial differentiation of selected cancer cells. They can decrease levels of cyclin D1 and E, inflammatory cytokines, and nuclear factor {kappa}B and increase expression of p21waf1 and p27kip1. Surprisingly, some or many of these effects may occur independently of PPAR{gamma}. Other data suggest that PPAR{gamma} may behave as a tumor suppressor gene, although several compelling murine models, paradoxically, suggest that under selected circumstances, PPAR{gamma} ligands may stimulate cancer formation. Nevertheless, the bulk of studies showed that PPAR{gamma} ligands do have antiproliferative activity against many transformed cells and may be helpful in the setting of adjuvant and chemopreventive treatments of several common tumors, including colon, prostate, and breast cancers.




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Copyright © 2003 by the American Association for Cancer Research.