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药物再利用治疗高级别浆液性卵巢癌。

Drugs Repurposing in High-Grade Serous Ovarian Cancer.

机构信息

Department of Life Sciences, University of Trieste, Via Giorgeri 1, 34127 Trieste, Italy

Department of Medical, Surgical and Health Sciences, University of Trieste, Cattinara Hospital, Strada di Fiume 447, 34149 Trieste, Italy

出版信息

Curr Med Chem. 2020;27(42):7222-7233. doi: 10.2174/0929867327666200713190520.

Abstract

BACKGROUND

Ovary Carcinoma (OC) is the most lethal gynecological neoplasm due to the late diagnoses and to the common development of resistance to platinum-based chemotherapy. Thus, novel therapeutic approaches are urgently required. In this regard, the strategy of drug repurposing is becoming attractive. By this approach, the effectiveness of a drug originally developed for another indication is tested in a different pathology. The advantage is that data about pharmacokinetic properties and toxicity are already available. Thus, in principle, it is possible to reduce research costs and to speed up drug usage/marketing.

RESULTS

Here, some noticeable examples of repurposed drugs for OC, such as amiodarone, ruxolitinib, statins, disulfiram, ormeloxifenem, and Quinacrine, are reported. Amiodarone, an antiarrhythmic agent, has shown promising anti-OC activity, although the systemic toxicity should not be neglected. The JAK inhibitor, Ruxolitinib, may be employed particularly in coadministration with standard OC therapy as it synergistically interacts with platinum-based drugs. Particularly interesting is the use of statin which represent one of the most commonly administered drugs in aged population to treat hypercholesterolemia. Disulfiram, employed in the treatment of chronic alcoholism, has shown anti-OC properties. Ormeloxifene, commonly used for contraception, seems to be promising, especially due to the negligible side effects. Finally, Quinacrine used as an antimicrobial and anti-inflammatory drug, is able to downregulate OC cell growth and promote cell death.

CONCLUSION

Whereas further testing in patients are necessary to better clarify the therapeutic potential of repurposed drugs for OC, it is believed that their use, better if combined with OC targeted delivery systems, can significantly contribute to the development of novel and effective anti-OC treatments.

摘要

背景

卵巢癌(OC)是最致命的妇科肿瘤,因为诊断较晚,并且普遍对铂类化疗产生耐药性。因此,迫切需要新的治疗方法。在这方面,药物再利用策略变得很有吸引力。通过这种方法,可以在不同的病理条件下测试最初用于其他适应症的药物的有效性。这样做的优点是,有关药代动力学特性和毒性的数据已经可用。因此,原则上可以降低研究成本并加快药物使用/上市的速度。

结果

这里报告了一些 OC 的再利用药物的显著例子,例如胺碘酮、鲁索替尼、他汀类药物、双硫仑、奥洛美芬和奎宁。抗心律失常药胺碘酮已显示出有希望的抗 OC 活性,尽管不应忽视其全身毒性。JAK 抑制剂鲁索替尼可与标准 OC 治疗联合使用,因为它与铂类药物具有协同作用,因此可能特别有用。特别有趣的是使用他汀类药物,他汀类药物是治疗高胆固醇血症的最常用药物之一,在老年人群中广泛使用。用于治疗慢性酒精中毒的双硫仑具有抗 OC 特性。通常用于避孕的奥洛美芬似乎很有前途,特别是因为副作用可以忽略不计。最后,用作抗菌和抗炎药物的奎宁能够下调 OC 细胞的生长并促进细胞死亡。

结论

虽然需要在患者中进行进一步的测试,以更好地阐明再利用药物对 OC 的治疗潜力,但人们认为,它们的使用(如果与 OC 靶向递送系统更好地结合)可以为开发新的有效的抗 OC 治疗方法做出重大贡献。

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