Fibroblast growth factor (FGF) receptor 4 (FGFR4) and its cognate ligand, FGF19, are implicated in a range of cellular processes, including differentiation, metabolism and proliferation. Indeed, their aberrant activation has been associated with the development of hepatic tumours. Despite great advances in early diagnosis and the development of new therapies, liver cancer is still associated with a high mortality rate, owing primarily to high molecular heterogeneity and unclear molecular targeting. The development of FGFR4 inhibitors is a promising tool in patients with concomitant supraphysiological levels of FGF19 and several clinical trials are testing these treatments for patients with advanced hepatocellular carcinoma (HCC). Conversely, using FGF19 analogues to activate FGFR4-KLOTHO β represents a novel therapeutic strategy in patients presenting with cholestatic liver disorders and non-alcoholic steatohepatitis, which could potentially prevent the development of metabolic HCC. Herein, we provide an overview of the currently available therapeutic options for targeting FGFR4 in HCC and other liver diseases, highlighting the need to carefully stratify patients and personalise therapeutic strategies.

成纤维细胞生长因子 (FGF) 受体 4 (FGFR4) 及其同源配体 FGF19 涉及一系列细胞过程，包括分化、代谢和增殖。事实上，它们的异常激活与肝肿瘤的发展有关。尽管在早期诊断和新疗法的开发方面取得了很大进展，但肝癌仍然与高死亡率相关，这主要是由于高分子异质性和不明确的分子靶向。FGFR4 抑制剂的开发对于同时存在超生理水平的 FGF19 的患者来说是一种很有前途的工具，并且一些临床试验正在测试这些治疗对晚期肝细胞癌 (HCC) 患者的治疗。反过来，使用 FGF19 类似物激活 FGFR4-KLOTHO β 代表了一种新的治疗策略，用于治疗胆汁淤积性肝病和非酒精性脂肪性肝炎的患者，这可能潜在地阻止代谢性 HCC 的发展。在此，我们概述了目前在 HCC 和其他肝病中靶向 FGFR4 的可用治疗选择，强调需要仔细对患者进行分层和个性化治疗策略。