Repurposing Drugs in Oncology (ReDO)-itraconazole as an anti-cancer agent.
Itraconazole, a common triazole anti-fungal drug in widespread clinical use, has evidence of clinical activity that is of interest in oncology. There is evidence that at the clinically relevant doses, itraconazole has potent anti-angiogenic activity, and that it can inhibit the Hedgehog signalling pathway and may also induce autophagic growth arrest. The evidence for these anticancer effects, in vitro, in vivo, and clinical are summarised, and the putative mechanisms of their action outlined. Clinical trials have shown that patients with prostate, lung, and basal cell carcinoma have benefited from treatment with itraconazole, and there are additional reports of activity in leukaemia, ovarian, breast, and pancreatic cancers. Given the evidence presented, a case is made that itraconazole warrants further clinical investigation as an anti- cancer agent. Additionally, based on the properties summarised previously, it is proposed that itraconazole may synergise with a range of other drugs to enhance the anti-cancer effect, and some of these possible combinations are presented in the supplementary materials accompanying this paper.
Anticancer Fund, 1853 Strombeek-Bever, Belgium ; The George Pantziarka TP53 Trust, London, KT1 2JP, UK.
Pan
P
Pantziarka
GlobalCures, Inc; Newton MA 02459, USA.
Vidula
V
Sukhatme
Anticancer Fund, 1853 Strombeek-Bever, Belgium.
Gauthier
G
Bouche
Anticancer Fund, 1853 Strombeek-Bever, Belgium.
Lydie
L
Meheus
GlobalCures, Inc; Newton MA 02459, USA ; Beth Israel Deaconess Medical Centre and Harvard Medical School, Boston, MA 02215, USA.
Vikas P
VP
Sukhatme
ReDO project; drug repurposing; hedgehog pathway inhibition; itraconazole