Restoring FXR expression as a novel treatment strategy in liver cancer and other liver disorders.

IF 4.6 2区医学 Q1 PHARMACOLOGY & PHARMACY

Expert Opinion on Therapeutic Targets Pub Date : 2025-04-01 DOI:10.1080/14728222.2025.2487465

Sosmitha Girisa, Babu Santha Aswani, Mukesh Kumar Manickasamy, Mangala Hegde, Mohammed S Alqahtani, Mohamed Abbas, Gautam Sethi, Ajaikumar B Kunnumakkara

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引用次数: 0

Abstract

Introduction: Liver cancer is a leading cause of cancer-associated mortality and is often linked to preexisting liver conditions. Emerging research demonstrates FXR dysregulation, particularly its reduced expression, in the pathogenesis of liver diseases, including inflammation, fibrosis, cholestatic disorders, metabolic dysregulation, and liver cancer. Therefore, this review explores the role of FXR and its agonists in mitigating these conditions.

Areas covered: This article summarizes FXR's involvement in liver disorders, primarily emphasizing on hepatic neoplasms, and examines the potential of FXR agonists in restoring FXR activity in liver diseases, thereby preventing their progression to liver cancer. The information presented is drawn from existing preclinical and clinical studies specific to each liver disorder, sourced from PubMed.

Expert opinion: It is well established that FXR expression is downregulated in liver disorders, contributing to disease progression. Notably, FXR agonists have demonstrated therapeutic potential in ameliorating liver diseases, including hepatocellular carcinoma. We believe that activating or restoring FXR expression with agonists offers significant promise for the treatment of liver cancer and other liver conditions. Therefore, FXR modulation by agonists, particularly in combination with other therapeutic agents, could lead to more targeted treatments, improving efficacy while reducing side effects.

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恢复FXR表达作为肝癌和其他肝脏疾病的新治疗策略。

肝癌是癌症相关死亡的主要原因，通常与先前存在的肝脏疾病有关。新兴研究表明，FXR失调，特别是其表达减少，在肝脏疾病的发病机制中，包括炎症、纤维化、胆汁淤积障碍、代谢失调和肝癌。因此，本综述探讨了FXR及其激动剂在缓解这些疾病中的作用。涉及领域：本文总结了FXR在肝脏疾病中的作用，主要强调肝脏肿瘤，并研究了FXR激动剂在肝脏疾病中恢复FXR活性的潜力，从而防止其发展为肝癌。所提供的信息来自PubMed上针对每种肝脏疾病的现有临床前和临床研究。专家意见：FXR在肝脏疾病中表达下调，促进疾病进展，这是公认的。值得注意的是，FXR激动剂已显示出改善肝脏疾病（包括肝细胞癌）的治疗潜力。我们相信，用激动剂激活或恢复FXR表达为肝癌和其他肝脏疾病的治疗提供了重要的希望。因此，激动剂调节FXR，特别是与其他治疗药物联合使用，可能会导致更有针对性的治疗，提高疗效，同时减少副作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Expert Opinion on Therapeutic Targets 医学-药学

CiteScore

8.90

自引率

1.70%

发文量

审稿时长

3 months

期刊介绍： The journal evaluates molecules, signalling pathways, receptors and other therapeutic targets and their potential as candidates for drug development. Articles in this journal focus on the molecular level and early preclinical studies. Articles should not include clinical information including specific drugs and clinical trials. The Editors welcome: Reviews covering novel disease targets at the molecular level and information on early preclinical studies and their implications for future drug development. Articles should not include clinical information including specific drugs and clinical trials. Original research papers reporting results of target selection and validation studies and basic mechanism of action studies for investigative and marketed drugs. The audience consists of scientists, managers and decision makers in the pharmaceutical industry, academic researchers working in the field of molecular medicine and others closely involved in R&D.