He Fangyu, Liu He, Zhao Fangcheng
Department of Hematology, The Second Hospital of Dalian Medical University, Dalian, China.
Department of Infection Control and Prevention, The Second Hospital of Dalian Medical University, Dalian, China.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Apr 23. doi: 10.1007/s00210-025-04144-5.
Hepatocellular carcinoma (HCC) remains a major global health challenge due to its aggressive nature and limited treatment options. This review aims to clarify the oncogenic role of FOXM1 in HCC and its potential as a therapeutic target. We examine how FOXM1 drives cancer development by regulating key cellular processes such as cell cycle progression, proliferation, metastasis, and therapy resistance. The review details mechanisms that control FOXM1 activity, including transcriptional regulation by upstream factors, post-transcriptional modulation via non-coding RNAs, and epigenetic modifications. We also explore how FOXM1 interacts with critical signaling pathways, such as AKT, p53, ERK, Hedgehog, STAT3, and Wnt/β-catenin, to promote metabolic reprogramming, angiogenesis, and the maintenance of cancer stem cell properties. In the therapeutic section, we assess emerging strategies that target FOXM1, including small-molecule inhibitors, proteasome inhibitors, and immunotherapeutic approaches, to improve treatment outcomes for HCC patients. This comprehensive review highlights the pivotal role of FOXM1 in HCC pathogenesis and provides novel avenues for targeted intervention.
肝细胞癌（HCC）因其侵袭性本质和有限的治疗选择，仍然是一项重大的全球健康挑战。本综述旨在阐明FOXM1在HCC中的致癌作用及其作为治疗靶点的潜力。我们研究了FOXM1如何通过调节细胞周期进程、增殖、转移和治疗抗性等关键细胞过程来驱动癌症发展。该综述详细介绍了控制FOXM1活性的机制，包括上游因子的转录调控、非编码RNA的转录后调节以及表观遗传修饰。我们还探讨了FOXM1如何与AKT、p53、ERK、Hedgehog、STAT3和Wnt/β-连环蛋白等关键信号通路相互作用，以促进代谢重编程、血管生成和癌症干细胞特性的维持。在治疗部分，我们评估了针对FOXM1的新兴策略，包括小分子抑制剂、蛋白酶体抑制剂和免疫治疗方法，以改善HCC患者的治疗效果。这一全面综述突出了FOXM1在HCC发病机制中的关键作用，并为靶向干预提供了新途径。
