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肺癌中α7烟碱型乙酰胆碱受体的靶向作用:见解、挑战与治疗策略

Targeting Alpha7 Nicotinic Acetylcholine Receptors in Lung Cancer: Insights, Challenges, and Therapeutic Strategies.

作者信息

Arunrungvichian Kuntarat, Vajragupta Opa, Hayakawa Yoshihiro, Pongrakhananon Varisa

机构信息

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand.

Unit of Compounds Library for Drug Discovery, Mahidol University, Bangkok 10400, Thailand.

出版信息

ACS Pharmacol Transl Sci. 2023 Dec 21;7(1):28-41. doi: 10.1021/acsptsci.3c00138. eCollection 2024 Jan 12.

Abstract

Alpha7 nicotinic acetylcholine receptor (α7 nAChR) is an ion-gated calcium channel that plays a significant role in various aspects of cancer pathogenesis, particularly in lung cancer. Preclinical studies have elucidated the molecular mechanism underlying α7 nAChR-associated lung cancer proliferation, chemotherapy resistance, and metastasis. Understanding and targeting this mechanism are crucial for developing therapeutic interventions aimed at disrupting α7 nAChR-mediated cancer progression and improving treatment outcomes. Drug research and discovery have determined natural compounds and synthesized chemical antagonists that specifically target α7 nAChR. However, approved α7 nAChR antagonists for clinical use are lacking, primarily due to challenges related to achieving the desired selectivity, efficacy, and safety profiles required for effective therapeutic intervention. This comprehensive review provided insights into the molecular mechanisms associated with α7 nAChR and its role in cancer progression, particularly in lung cancer. Furthermore, it presents an update on recent evidence about α7 nAChR antagonists and addresses the challenges encountered in drug research and discovery in this field.

摘要

α7烟碱型乙酰胆碱受体(α7 nAChR)是一种离子门控钙通道,在癌症发病机制的各个方面,尤其是肺癌中发挥着重要作用。临床前研究已经阐明了α7 nAChR相关肺癌增殖、化疗耐药和转移的分子机制。理解并针对这一机制对于开发旨在破坏α7 nAChR介导的癌症进展并改善治疗结果的治疗干预措施至关重要。药物研究与发现已经确定了特异性靶向α7 nAChR的天然化合物和合成化学拮抗剂。然而,目前缺乏已获批用于临床的α7 nAChR拮抗剂,主要是因为在实现有效治疗干预所需的理想选择性、疗效和安全性方面存在挑战。这篇综述深入探讨了与α7 nAChR相关的分子机制及其在癌症进展,特别是肺癌进展中的作用。此外,它还介绍了有关α7 nAChR拮抗剂的最新证据,并探讨了该领域药物研究与发现中遇到的挑战。

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