仑伐替尼的作用机制及其在HCC治疗中的应用

The Action Mechanism of Lenvatinib and Its Application in the Treatment of Hepatocellular Carcinoma (HCC)

摘要: 肝细胞癌(Hepatocellular Carcinoma, HCC)是一种在全球范围内广泛发生的恶性肿瘤，其治疗面临着显著的挑战。仑伐替尼(Lenvatinib)作为一种多靶点的酪氨酸激酶抑制剂，已成为HCC的一线治疗药物。然而，其临床疗效常常受到耐药性出现的限制。近年来，研究者们对耐药性形成的多种因素进行了深入研究，这些因素包括靶点突变、信号通路异常活化、表观遗传调控失常以及肿瘤微环境的重塑等。此外，耐药相关的生物标志物的识别为个体化治疗的实施提供了潜在的依据。目前，针对耐药机制的治疗策略，如联合用药、靶向肿瘤微环境及免疫治疗等，显示出一定的应用前景。本文系统性地综述了仑伐替尼耐药的分子机制及其应对策略，旨在为改善HCC患者的临床预后提供理论支持和实践指导。

Abstract: Hepatocellular Carcinoma (HCC) is a malignant tumor that occurs widely around the world, and its treatment faces significant challenges. Lenvatinib, as a multi-targeted tyrosine kinase inhibitor, has become a first-line treatment drug for HCC. However, its clinical efficacy is often limited by the emergence of drug resistance. In recent years, researchers have conducted in-depth studies on the various factors contributing to the formation of drug resistance, including target mutations, abnormal activation of signaling pathways, epigenetic regulatory disorders, and remodeling of the tumor microenvironment. In addition, the identification of drug resistance-related biological markers provides potential evidence for the implementation of personalized treatment. Currently, treatment strategies targeting drug resistance mechanisms, such as combination therapy, targeting the tumor microenvironment, and immunotherapy, show certain application prospects. This article systematically reviews the molecular mechanisms of Lenvatinib resistance and its countermeasures, aiming to provide theoretical support and practical guidance for improving the clinical prognosis of HCC patients.