ITRACONAZOLE IN mCRPC
With a desire to increase efficiency in the pharmaceutical development industry a ‘drug library’ with over 3,000 existing compounds was created, enabling in vitro screening of old drugs for novel biological functions. The library, having been screened for agents that may inhibit angiogenesis, (a potentially important target of prostate cancer therapies) found an unexpected ‘hit’ in itraconazole which was found to inhibit endothelial cell proliferation in vitro and to impede endothelial cell migration and capillary tube formation.
In vivo, itraconazole was found to inhibit neovascularization in a mouse MatrigelTM model, to delay tumor growth in a castration-resistant xenograft mouse model, and to inhibit metastasis in the AT6.3 prostate cancer mouse model.
Itraconazole was also discovered to potentially inhibit Hedgehog (Hh) signaling, a developed pathway regulating epithelial-mesenchymal interactions, cell survival, and angiogenesis. To this end, in vitro studies showed that itraconazole inhibited proliferation of the Hh reported cell line Shh-Light2 by antagonizing Smoothened, additionally inducing tumor growth. – JHU, Repurposing Itraconazole.., 2013