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PPAR-alpha's in cancer

In a paper published in the Proceedings of the National Academy of Sciences, Harvard University researchers demonstrated an anticancer effect in mice taking oral doses of the generic dyslipidemia drug fenofibrate.1 The good safety profile of the peroxisome proliferation-activated receptor-a agonist has led the researchers to begin a Phase II trial.

Fenofibrate's antiangiogenic effects were first identified in 2003,2 but it was not until last year that researchers looked at the effects of peroxisome proliferation-activated receptor-a (PPAR-a) agonists in primary tumors.3 The PNAS paper confirms these results and goes a step further, showing that fenofibrate can slow tumor growth at doses comparable to those doctors prescribe for the drug's approved lipid-lowering indication.

In vitro, the PPAR-a agonists fenofibrate and gemfibrozil and the pan-PPAR agonist bezafibrate all inhibited proliferation of endothelial cells as well as VEGF-stimulated endothelial cell migration. The three drugs are approved in the U.S., Europe and elsewhere to treat dyslipidemia.

Fenofibrate showed the strongest effect. A 200 mg/kg oral daily dose inhibited growth of melanoma, lung cancer, glioblastoma and fibrosarcoma tumors by 58-72% at 3-4 weeks in mice with cancer xenografts.

Knocking out PPAR-a in mice markedly reduced the antitumor

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