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RC : The peoxisome proliferator-activated receptors (what a mouthful! The acronym is PPAR) are members of a superfamily of nuclear hormone receptors that play a diverse regulatory role on metabolism including the regulation of lipid and sugar metabolism. Activation of PPAR receptors elicit anti-inflammatory and anti-cancer effects (via apoptosis and antiangiogenesis as well as direct antiproliferation). Of the isoforms of PPAR family so far identified, the PPAR-gamma isoform is especially promising as a therapeutic possibility in cancer. PPAR-gamma agonist are now in clinical use as anti-diabetic drugs (e.g. rosiglitazone) because activation of PPAR-gamma lowers serum glucose in diabetics. In vitro and animal* studies have documented the anticancer effects of PPAR-gamma agonists in a broad array of tumors including prostate*, thyroid*, gastric, colon*, pancreas, liver, breast*, lung, brain and neuroblastoma. To date, clinical trials with rosiglitazone have shown efficacy in PPAR agonist treatment with prostate cancer and liposarcoma. Results are particularly impressive in prostate cancer cases wher troglitazone 800mg a day stabilized PSA in patients with advanced prostate cancer. A nice review of PPAR and cancer was recently published in Lancet Oncology.

We have been using a cocktail of cox-2 antagonist, PPAR gamma agonist and statins where clinically appropriate to treat various cancers and have noted general tolerability of this approach even in non-diabetics. From our experience, it is doubtful if PPAR gamma agonists given alone has much efficacy in treating established cancer, but a cocktail approach with other antiangiogenic and apoptosis agents can be especially useful in chemoprevention (See Ref) and secodary prevention or adjunct treatment of certain cancers. It has already been proposed as a viable preventative approach in prostate (See Ref) as well as breast (See Ref) cancer.