肾素血管紧张素系统抑制剂和二甲双胍在胶质母细胞瘤治疗中的作用:综述。

IF 2.7 4区 医学 Q3 ONCOLOGY Cancer Chemotherapy and Pharmacology Pub Date : 2024-07-01 Epub Date: 2024-06-25 DOI:10.1007/s00280-024-04686-0
Sashana Dixon, Ann Tenneil O'connor, Chloe Brooks-Noreiga, Michelle A Clark, Arkene Levy, Ana M Castejon
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摘要

多形性胶质母细胞瘤(GBM)是一种侵袭性极强的不治之症,美国每年约有 10,000 人死于这种疾病。尽管目前的治疗方法包括手术、化疗和放疗,但复发率仍然很高。在接受标准治疗的同时,同时服用肾素血管紧张素抑制剂(RAS)等抗高血压药物或二甲双胍等抗糖尿病药物的患者病情明显好转。在体外和体内研究中已观察到 RAS 抑制剂和二甲双胍的抗肿瘤作用。虽然临床试验结果不一,但使用 RAS 抑制剂和二甲双胍作为 GBM 辅助治疗的潜力仍然很好。然而,有证据表明这些药物具有多模式抗肿瘤作用,尤其是针对几种癌症标志物。在这篇综述中,我们重点介绍了在 GBM 标准疗法中添加 RAS 抑制剂和二甲双胍的多药鸡尾酒的临床研究结果。此外,我们还强调了这些安全性极佳的再利用药物可能产生抗肿瘤作用的分子机制。抑制 RAS 可在 GBM 中产生抗炎、抗血管生成和免疫敏感效应。然而,二甲双胍主要通过激活AMP激活蛋白激酶来促进抗迁移、抗增殖和促凋亡作用。此外,我们还讨论了二甲双胍在靶向 GBM 细胞以及 GBM 相关干细胞方面的潜力。最后,我们总结了一些药物相互作用,这些相互作用可能会产生相加或拮抗作用,从而导致不良反应并影响治疗效果。
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Role of renin angiotensin system inhibitors and metformin in Glioblastoma Therapy: a review.

Glioblastoma multiforme (GBM) is a highly aggressive and incurable disease accounting for about 10,000 deaths in the USA each year. Despite the current treatment approach which includes surgery with chemotherapy and radiation therapy, there remains a high prevalence of recurrence. Notable improvements have been observed in persons receiving concurrent antihypertensive drugs such as renin angiotensin inhibitors (RAS) or the antidiabetic drug metformin with standard therapy. Anti-tumoral effects of RAS inhibitors and metformin have been observed in in vitro and in vivo studies. Although clinical trials have shown mixed results, the potential for the use of RAS inhibitors and metformin as adjuvant GBM therapy remains promising. Nevertheless, evidence suggest that these drugs exert multimodal antitumor actions; by particularly targeting several cancer hallmarks. In this review, we highlight the results of clinical studies using multidrug cocktails containing RAS inhibitors and or metformin added to standard therapy for GBM. In addition, we highlight the possible molecular mechanisms by which these repurposed drugs with an excellent safety profile might elicit their anti-tumoral effects. RAS inhibition elicits anti-inflammatory, anti-angiogenic, and immune sensitivity effects in GBM. However, metformin promotes anti-migratory, anti-proliferative and pro-apoptotic effects mainly through the activation of AMP-activated protein kinase. Also, we discussed metformin's potential in targeting both GBM cells as well as GBM associated-stem cells. Finally, we summarize a few drug interactions that may cause an additive or antagonistic effect that may lead to adverse effects and influence treatment outcome.

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来源期刊
CiteScore
6.10
自引率
3.30%
发文量
116
审稿时长
2.5 months
期刊介绍: Addressing a wide range of pharmacologic and oncologic concerns on both experimental and clinical levels, Cancer Chemotherapy and Pharmacology is an eminent journal in the field. The primary focus in this rapid publication medium is on new anticancer agents, their experimental screening, preclinical toxicology and pharmacology, single and combined drug administration modalities, and clinical phase I, II and III trials. It is essential reading for pharmacologists and oncologists giving results recorded in the following areas: clinical toxicology, pharmacokinetics, pharmacodynamics, drug interactions, and indications for chemotherapy in cancer treatment strategy.
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