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

James Kim, Jean Y. Tang, Ruoyu Gong, Jynho Kim, John J. Lee, Karl V. Clemons, Curtis R. Chong, Kris S. Chang, Mark Fereshteh, Dale Gardner, Tannishtha Reya, Jun O. Liu, Ervin H. Epstein, David A. Stevens, Philip A. Beachy

Research output: Contribution to journalArticle

295 Citations (Scopus)

Abstract

In a screen of drugs previously tested in humans we identified itraconazole, a systemic antifungal, as a potent antagonist of the Hedgehog (Hh) signaling pathway that acts by a mechanism distinct from its inhibitory effect on fungal sterol biosynthesis. Systemically administered itraconazole, like other Hh pathway antagonists, can suppress Hh pathway activity and the growth of medulloblastoma in a mouse allograft model and does so at serum levels comparable to those in patients undergoing antifungal therapy. Mechanistically, itraconazole appears to act on the essential Hh pathway component Smoothened (SMO) by a mechanism distinct from that of cyclopamine and other known SMO antagonists, and prevents the ciliary accumulation of SMO normally caused by Hh stimulation.

Original languageEnglish (US)
Pages (from-to)388-399
Number of pages12
JournalCancer Cell
Volume17
Issue number4
DOIs
StatePublished - Apr 13 2010

Fingerprint

Itraconazole
Hedgehogs
Growth
Neoplasms
Medulloblastoma
Sterols
Allografts
Serum
Pharmaceutical Preparations

Keywords

  • CELLCYCLE
  • CHEMBIO

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

Cite this

Kim, J., Tang, J. Y., Gong, R., Kim, J., Lee, J. J., Clemons, K. V., ... Beachy, P. A. (2010). Itraconazole, a Commonly Used Antifungal that Inhibits Hedgehog Pathway Activity and Cancer Growth. Cancer Cell, 17(4), 388-399. https://doi.org/10.1016/j.ccr.2010.02.027

Itraconazole, a Commonly Used Antifungal that Inhibits Hedgehog Pathway Activity and Cancer Growth. / Kim, James; Tang, Jean Y.; Gong, Ruoyu; Kim, Jynho; Lee, John J.; Clemons, Karl V.; Chong, Curtis R.; Chang, Kris S.; Fereshteh, Mark; Gardner, Dale; Reya, Tannishtha; Liu, Jun O.; Epstein, Ervin H.; Stevens, David A.; Beachy, Philip A.

In: Cancer Cell, Vol. 17, No. 4, 13.04.2010, p. 388-399.

Research output: Contribution to journalArticle

Kim, J, Tang, JY, Gong, R, Kim, J, Lee, JJ, Clemons, KV, Chong, CR, Chang, KS, Fereshteh, M, Gardner, D, Reya, T, Liu, JO, Epstein, EH, Stevens, DA & Beachy, PA 2010, 'Itraconazole, a Commonly Used Antifungal that Inhibits Hedgehog Pathway Activity and Cancer Growth', Cancer Cell, vol. 17, no. 4, pp. 388-399. https://doi.org/10.1016/j.ccr.2010.02.027
Kim, James ; Tang, Jean Y. ; Gong, Ruoyu ; Kim, Jynho ; Lee, John J. ; Clemons, Karl V. ; Chong, Curtis R. ; Chang, Kris S. ; Fereshteh, Mark ; Gardner, Dale ; Reya, Tannishtha ; Liu, Jun O. ; Epstein, Ervin H. ; Stevens, David A. ; Beachy, Philip A. / Itraconazole, a Commonly Used Antifungal that Inhibits Hedgehog Pathway Activity and Cancer Growth. In: Cancer Cell. 2010 ; Vol. 17, No. 4. pp. 388-399.
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