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研究动态:右美托咪定在癌症治疗中的应用。

Trial watch: dexmedetomidine in cancer therapy.

机构信息

Equipe Labellisée Par La Ligue Contre Le Cancer, Université de Paris, Sorbonne Université, Paris, France.

Metabolomics and Cell Biology Platforms, Gustave Roussy, Université Paris Saclay, Villejuif, France.

出版信息

Oncoimmunology. 2024 Mar 11;13(1):2327143. doi: 10.1080/2162402X.2024.2327143. eCollection 2024.

Abstract

Dexmedetomidine (DEX) is a highly selective α2-adrenoceptor agonist that is widely used in intensive and anesthetic care for its sedative and anxiolytic properties. DEX has the capacity to alleviate inflammatory pain while limiting immunosuppressive glucocorticoid stress during major surgery, thus harboring therapeutic benefits for oncological procedures. Recently, the molecular mechanisms of DEX-mediated anticancer effects have been partially deciphered. Together with additional preclinical data, these mechanistic insights support the hypothesis that DEX-induced therapeutic benefits are mediated the stimulation of adaptive anti-tumor immune responses. Similarly, published clinical trials including ancillary studies described an immunostimulatory role of DEX during the perioperative period of cancer surgery. The impact of DEX on long-term patient survival remains elusive. Nevertheless, DEX-mediated immunostimulation offers an interesting therapeutic option for onco-anesthesia. Our present review comprehensively summarizes data from preclinical and clinical studies as well as from ongoing trials with a distinct focus on the role of DEX in overcoming (tumor microenvironment (TME)-imposed) cancer therapy resistance. The objective of this update is to guide clinicians in their choice toward immunostimulatory onco-anesthetic agents that have the capacity to improve disease outcome.

摘要

右美托咪定(DEX)是一种高度选择性的α2-肾上腺素受体激动剂,因其具有镇静和抗焦虑特性,在重症监护和麻醉护理中被广泛应用。DEX 具有缓解炎症性疼痛的能力,同时在大手术期间限制免疫抑制糖皮质激素应激,因此对肿瘤治疗具有治疗益处。最近,DEX 介导的抗癌作用的分子机制已部分阐明。这些机制上的见解与其他临床前数据一起,支持 DEX 诱导的治疗益处是通过刺激适应性抗肿瘤免疫反应来介导的假说。同样,已发表的临床试验包括辅助研究描述了 DEX 在癌症手术围手术期的免疫刺激作用。DEX 对长期患者生存的影响仍不清楚。然而,DEX 介导的免疫刺激为肿瘤麻醉学提供了一个有趣的治疗选择。我们目前的综述全面总结了来自临床前和临床研究以及正在进行的试验的数据,重点关注 DEX 在克服(肿瘤微环境(TME)引起的)癌症治疗耐药性方面的作用。本次更新的目的是指导临床医生选择具有改善疾病结局能力的免疫刺激肿瘤麻醉药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd70/10936656/5365b6b39c12/KONI_A_2327143_F0001_OC.jpg

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