Department of Biochemistry and Pharmacology, School of Medicine, Faculdade de Medicina de Marília (FAMEMA), Marília, São Paulo, 17519-030, Brazil.
Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Marília (UNIMAR), Marília, São Paulo, 17525-902, Brazil.
Naunyn Schmiedebergs Arch Pharmacol. 2024 Apr;397(4):2067-2082. doi: 10.1007/s00210-023-02792-z. Epub 2023 Oct 21.
The potential benefits of adiponectin replacement therapy extend to numerous human diseases, with current research showing particular interest in its effectiveness against specific cancer forms, especially hormone-related. However, limitations in the pharmacological use of the intact protein have led to a focus on alternative options. AdipoRon is an extensively studied non-peptidic drug candidate for adiponectin replacement therapy. While researchers have explored the efficacy and therapeutic applications of AdipoRon in various disease conditions, their effects against cancer models advanced more, with no review regarding AdipoRon's efficacy against hormone-related cancers being published. The present systematic review aims to fill this gap. Preclinical evidence was compiled from PubMed, EMBASE, COCHRANE, and Google Scholar following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and the manuscript's quality assessment was conducted using the Joanna Briggs Institute (JBI) Checklist Critical Appraisal Tool for Systematic Reviews' Quality. The included nine studies incorporated various cell and animal models of the pancreas, gynaecological system, and osteosarcoma cancers. AdipoRon demonstrated effectiveness against pancreatic cancer by activating p44/42 MAPK, mitochondrial dysfunction, and AMPK-mediated inhibition of ACC1. In gynaecological cancers, it exhibited promising anticancer effects through the activation of AMPK, potential inhibition of mTOR, and modulation of the SET1B/BOD1/AdipoR1 signaling cascade. Against osteosarcoma, AdipoRon worked by perturbing ERK1/2 signaling and reducing p70S6K phosphorylation. AdipoRon shows promise in preclinical studies, but human trials are crucial for clinical safety and effectiveness. Caution is needed due to potential off-target effects, especially in cancer therapy with multi-target approaches. Structural biology and computational methods can help predict these effects.
脂联素替代疗法的潜在益处扩展到许多人类疾病，目前的研究特别关注其对特定癌症形式的有效性，尤其是与激素相关的癌症。然而，完整蛋白在药理学应用上的局限性导致人们关注替代方案。AdipoRon 是一种经过广泛研究的非肽类药物候选物，可用于脂联素替代疗法。虽然研究人员已经在各种疾病条件下探索了 AdipoRon 的疗效和治疗应用，但它们对癌症模型的影响更为深入，尚无关于 AdipoRon 对激素相关癌症疗效的综述发表。本系统评价旨在填补这一空白。根据系统评价和荟萃分析的首选报告项目 (PRISMA) 指南，从 PubMed、EMBASE、COCHRANE 和 Google Scholar 中汇编了临床前证据，并使用 Joanna Briggs 研究所 (JBI) 清单对纳入研究进行了质量评估系统评价的关键评估工具。纳入的九项研究纳入了胰腺、妇科系统和骨肉瘤的各种细胞和动物模型。AdipoRon 通过激活 p44/42 MAPK、线粒体功能障碍和 AMPK 介导的 ACC1 抑制来对抗胰腺癌。在妇科癌症中，它通过激活 AMPK、潜在抑制 mTOR 和调节 SET1B/BOD1/AdipoR1 信号级联发挥有前途的抗癌作用。针对骨肉瘤，AdipoRon 通过扰乱 ERK1/2 信号和减少 p70S6K 磷酸化起作用。AdipoRon 在临床前研究中显示出前景，但人体试验对于临床安全性和有效性至关重要。由于潜在的脱靶效应，特别是在具有多靶点方法的癌症治疗中，需要谨慎。结构生物学和计算方法可以帮助预测这些效应。
