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超越心脏病学的界限:心血管系统相关药物尚未开发的抗癌特性。

Beyond the boundaries of cardiology: Still untapped anticancer properties of the cardiovascular system-related drugs.

机构信息

Greater Poland Oncology Center, Hospital Pharmacy, 15 Garbary Street, 61-866, Poznań, Poland.

Masters Ltd, Wysogotowo, 30 Skórzewska Street, 62-081, Przeźmierowo, Poland.

出版信息

Pharmacol Res. 2019 Sep;147:104326. doi: 10.1016/j.phrs.2019.104326. Epub 2019 Jul 21.

Abstract

Cardiovascular disorders and cancer are the most common chronic diseases, frequently coexistent and interdependent. Based on their common etiology and molecular background, the hypothesis on the potential anti-cancer activity of cardiological drugs appeared, mainly in response to the necessity of increasing the efficacy of existing oncological treatment schemes. In fact, cancer is known to induce the profound malfunction of typical cardiovascular-regulating systems, including the renin-angiotensin system, sympathetic nervous system and coagulation cascade. Therefore, in this review we have analyzed the available preclinical and clinical data on the repurposing potential of the following classes of cardiology drugs: angiotensin converting-enzyme inhibitors, angiotensin receptor blockers, beta blockers, statins and heparins. All of them have been shown to attenuate cancer development: the renin-angiotensin system inhibitors primarily by reducing inflammation, angiogenesis and immunosuppression, beta blockers by repressing migration and metastasis, heparins by decreasing metastasis and statins by influencing cell growth, apoptosis, migration and angiogenesis. We also have discussed the specific mechanisms of anticancer action for each group and then suggestions on their potential clinical use have been presented. Nonetheless, the establishment of strong indications for repurposing procedure, both individually and collectively, is unfeasible at the moment due to insufficient clinical data and therefore further investigations in this context are necessary and encouraged.

摘要

心血管疾病和癌症是最常见的慢性疾病,常常同时存在且相互依存。基于它们共同的病因和分子背景,出现了心血管药物潜在抗癌活性的假说,主要是为了提高现有肿瘤治疗方案的疗效。事实上,众所周知,癌症会导致典型的心血管调节系统的严重功能障碍,包括肾素-血管紧张素系统、交感神经系统和凝血级联。因此,在这篇综述中,我们分析了以下几类心脏病药物的重新定位潜力的现有临床前和临床数据:血管紧张素转换酶抑制剂、血管紧张素受体阻滞剂、β受体阻滞剂、他汀类药物和肝素。所有这些药物都被证明可以抑制癌症的发展:肾素-血管紧张素系统抑制剂主要通过减少炎症、血管生成和免疫抑制,β受体阻滞剂通过抑制迁移和转移,肝素通过减少转移,他汀类药物通过影响细胞生长、凋亡、迁移和血管生成。我们还讨论了每个组的抗癌作用的具体机制,然后提出了关于它们潜在临床应用的建议。然而,由于临床数据不足,目前单独和集体重新定位程序的适应证的建立是不可行的,因此在这方面需要并鼓励进一步的研究。

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