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Prostate Cancer Research

Itraconazole, a Commonly Used Antifungal that Inhibits Hedgehog Pathway Activity and Cancer Growth

The prostate cancer research field is fast paced. PCF’s Science Department routinely holds scientific discussions with leading cancer researchers to stay abreast of the most recent prostate cancer publications. These meetings keep PCF at the cutting edge of prostate cancer research. This section provides summaries of these “Journal Club” meetings.

Presenters: James Kim, MD
Post-Doctoral Fellow
Stanford University

Phil Beachy, PhD
Howard Hughes Investigator
Ernest and Amelia Gallo Professor
Stanford University

Paper: Itraconazole, a Commonly Used Antifungal that Inhibits Hedgehog Pathway Activity and Cancer Growth (Kim, J., Tang, J.Y., Gong, R., Kim, J., Lee, J.J., Clemons, K.V., Chong, C.R., Chang, K.S., Fereshteh, M., Gardner, D., Reya, T., Liu, J.O., Epstein, E.H., Stevens, D.A., Beachy, P.A. Cancer Cell, 2010 April 13. 17:388-399.)

Summary: A signaling pathway called Hedgehog, which is important for many normal cell functions, has been implicated in cancer (including prostate cancer) initiation and metastasis when active at inappropriately high levels. There is significant discovery and development of inhibitors of the Hedgehog pathway as a target to treat human cancers. Early studies by Dr. Beachy set the stage for this flurry of activity.

Drs. Phil Beachy and James Kim initiated this project to identify FDA-approved drugs that have activity against the Hedgehog pathway. The goal was to streamline a route to therapy for patients who could benefit from agents that target the Hedgehog pathway. The team of researchers screened ~3,000 FDA-approved compounds and found several that block Hedgehog signaling. In this report they describe the medicine called Itraconazole, which is approved for use as an anti-fungal agent. Using two different mouse tumor models (medulloblastoma and basal cell carcinoma) the authors showed that Itraconazole could significantly slow the growth of tumors. Since, Itraconazole also functions by blocking cholesterol synthesis (this mechanisms is responsible for killing fungus) the investigators tested whether cholesterol lowering drugs, like statins, have an effect on the Hedgehog signaling. They found that Lovastatin can block the Hedgehog pathway. These findings are thought provoking given the recent epidemiologic studies showing that prostate cancer patients taking statins may have better overall outcomes than patients not taking statins. Future studies aimed at understanding the link between statins and the hedgehog pathway may uncover a new treatment strategy for prostate cancer.

PCF funding: Dr. Beachy was awarded Competitive Awards in 1999, 2000 and 2005.

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