Journal of Hepatocellular Carcinoma (Jul 2023)

Application and Resistance Mechanisms of Lenvatinib in Patients with Advanced Hepatocellular Carcinoma

  • Tao M,
  • Han J,
  • Shi J,
  • Liao H,
  • Wen K,
  • Wang W,
  • Mui S,
  • Li H,
  • Yan Y,
  • Xiao Z

Journal volume & issue
Vol. Volume 10
pp. 1069 – 1083

Abstract

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Meng Tao,1,2 Jing Han,3 Juanyi Shi,1,2 Hao Liao,1,2 Kai Wen,1,2 Weidong Wang,1,2 Sintim Mui,1,2 Huoming Li,1,2 Yongcong Yan,1,2 Zhiyu Xiao1,2 1Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, People’s Republic of China; 3Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, People’s Republic of ChinaCorrespondence: Yongcong Yan; Zhiyu Xiao, Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Yanjiang West Road #107, Guangzhou, 510120, People’s Republic of China, Tel +86-15800039176 ; +86-13682283695, Fax +86 20 34071073, Email [email protected]; [email protected]: Lenvatinib, a multitargeted tyrosine kinase inhibitor (TKI), is one of the preferred targeted drugs for the treatment of advanced hepatocellular carcinoma (aHCC). Since the REFLECT study showed that lenvatinib was noninferior to sorafenib in overall survival (OS), lenvatinib monotherapy has been widely used for aHCC. Moreover, lenvatinib combination therapy, especially lenvatinib combined with immune checkpoint inhibitors (ICIs), has shown more encouraging clinical results. However, drug development and comprehensive treatment have not significantly improved the prognosis, and lenvatinib resistance is often encountered in treatment. The underlying molecular mechanism of lenvatinib resistance is still unclear, and studies to solve drug resistance are ongoing. The molecular mechanisms of lenvatinib resistance in patients with aHCC include the regulation of signaling pathways, the regulation of noncoding RNAs, the impact of the immune microenvironment, tumor stem cell activation and other mechanisms. This review aims to (1) summarize the progress of lenvatinib in treating aHCC, (2) delineate the known lenvatinib resistance mechanisms of current therapy, and (3) describe the development of therapeutic methods intended to overcome these resistance mechanisms.Keywords: lenvatinib, application, drug resistance, hepatocellular carcinoma

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