The role of tumor microenvironment in lenvatinib resistance of hepatocellular carcinoma

IF 2.6 4区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Clinics and research in hepatology and gastroenterology Pub Date : 2025-07-01 DOI:10.1016/j.clinre.2025.102642

Yao Jiang , Yingchen Huang , Xin Hu , Guanrong Chen , Ronggao Chen , Xiao Xu

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Abstract

In 2018, lenvatinib was approved as a first-line treatment of advanced hepatocellular carcinoma (HCC). Despite the initial success, its effectiveness in long-term clinical practice is restricted by the emergence of drug resistance. The tumor microenvironment (TME), comprised of various cellular and non-cellular components,collectively drives HCC growth, invasion, and resistance to treatment. Currently, numerous investigations have elucidated that lenvatinib exerts its influence on a multitude of targets within the TME. Moreover, many components of the TME can affect the sensitivity of lenvatinib either directly through interactions or promoting tumor immune evasion. TME plays a crucial role in the development of lenvatinib resistance (LR) in HCC. This review presents an overview on the role of the TME in LR of HCC. Furthermore, it explores therapeutic strategies targeting the TME for overcoming LR. These may improve the efficacy of lenvatinib and the prognosis of advanced HCC patients.

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肿瘤微环境在肝癌lenvatinib耐药中的作用。

2018年，lenvatinib被批准作为晚期肝细胞癌（HCC）的一线治疗药物。尽管最初取得了成功，但其在长期临床实践中的有效性受到耐药性出现的限制。肿瘤微环境（tumor microenvironment， TME）由各种细胞和非细胞成分组成，共同驱动HCC的生长、侵袭和对治疗的抵抗。目前，许多研究已经阐明lenvatinib对TME内的众多靶点施加影响。此外，TME的许多成分可以通过相互作用或促进肿瘤免疫逃避直接影响lenvatinib的敏感性。TME在HCC中lenvatinib耐药（LR）的发展中起着至关重要的作用。本文综述了TME在肝细胞癌LR中的作用。此外，它还探讨了针对TME克服LR的治疗策略。这些可能会改善lenvatinib的疗效和晚期HCC患者的预后。

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

Clinics and research in hepatology and gastroenterology GASTROENTEROLOGY & HEPATOLOGY-

CiteScore

4.30

自引率

3.70%

发文量

198

审稿时长

42 days

期刊介绍： Clinics and Research in Hepatology and Gastroenterology publishes high-quality original research papers in the field of hepatology and gastroenterology. The editors put the accent on rapid communication of new research and clinical developments and so called "hot topic" issues. Following a clear Editorial line, besides original articles and case reports, each issue features editorials, commentaries and reviews. The journal encourages research and discussion between all those involved in the specialty on an international level. All articles are peer reviewed by international experts, the articles in press are online and indexed in the international databases (Current Contents, Pubmed, Scopus, Science Direct). Clinics and Research in Hepatology and Gastroenterology is a subscription journal (with optional open access), which allows you to publish your research without any cost to you (unless you proactively chose the open access option). Your article will be available to all researchers around the globe whose institution has a subscription to the journal.