Girisa Sosmitha, Aswani Babu Santha, Manickasamy Mukesh Kumar, Hegde Mangala, Alqahtani Mohammed S, Abbas Mohamed, Sethi Gautam, Kunnumakkara Ajaikumar B
Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati (IITG), Guwahati, India.
Radiological Sciences Department, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia.
Expert Opin Ther Targets. 2025 Apr-May;29(4-5):193-221. doi: 10.1080/14728222.2025.2487465. Epub 2025 May 11.
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.
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.
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.
肝癌是癌症相关死亡的主要原因，且常与先前存在的肝脏疾病相关。新兴研究表明，在包括炎症、纤维化、胆汁淤积性疾病、代谢失调和肝癌在内的肝脏疾病发病机制中，法尼醇X受体（FXR）失调，尤其是其表达降低。因此，本综述探讨了FXR及其激动剂在缓解这些病症中的作用。
本文总结了FXR在肝脏疾病中的作用，主要侧重于肝脏肿瘤，并研究了FXR激动剂在恢复肝脏疾病中FXR活性从而预防其进展为肝癌方面的潜力。所呈现的信息来自于从PubMed获取的针对每种肝脏疾病的现有临床前和临床研究。
众所周知，FXR表达在肝脏疾病中下调，促进疾病进展。值得注意的是，FXR激动剂已在改善包括肝细胞癌在内的肝脏疾病方面显示出治疗潜力。我们认为，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带来了巨大希望。因此，激动剂对FXR的调节，尤其是与其他治疗药物联合使用，可能会带来更有针对性的治疗，提高疗效同时减少副作用。
