Pantziarka Pan, Sukhatme Vidula, Bouche Gauthier, Meheus Lydie, Sukhatme Vikas P
Anticancer Fund, 1853 Strombeek-Bever, Belgium ; The George Pantziarka TP53 Trust, London, KT1 2JP, UK.
GlobalCures, Inc; Newton MA 02459, USA.
Ecancermedicalscience. 2015 Apr 15;9:521. doi: 10.3332/ecancer.2015.521. eCollection 2015.
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.
伊曲康唑是一种临床广泛使用的常见三唑类抗真菌药物，有证据表明其临床活性在肿瘤学领域具有重要意义。有证据显示，在临床相关剂量下，伊曲康唑具有强大的抗血管生成活性，能够抑制刺猬信号通路，还可能诱导自噬性生长停滞。本文总结了伊曲康唑在体外、体内及临床方面的抗癌作用证据，并概述了其假定的作用机制。临床试验表明，前列腺癌、肺癌和基底细胞癌患者接受伊曲康唑治疗后均有获益，此外还有关于伊曲康唑对白血病、卵巢癌、乳腺癌和胰腺癌有治疗活性的报道。基于所提供的证据，有理由认为伊曲康唑作为一种抗癌药物值得进一步开展临床研究。此外，根据之前总结的特性，有人提出伊曲康唑可能与一系列其他药物协同作用以增强抗癌效果，本文的补充材料中列出了一些可能的联合用药方案。
