TITLE:
Latest Research Progress on the Mechanisms of Lenvatinib Resistance
AUTHORS:
Ding Qi, Yaoxiang Wu, Yong Li
KEYWORDS:
Hepatocellular Carcinoma, Lenvatinib, Drug Resistance
JOURNAL NAME:
Journal of Biosciences and Medicines,
Vol.12 No.12,
December
24,
2024
ABSTRACT: Hepatocellular carcinoma (HCC) poses a formidable obstacle to global health. Modern medicine has made tremendous efforts to address the threat posed by HCC, but most current treatment methods are only effective for early-stage HCC, whereas the majority of HCC cases are diagnosed at an advanced stage. Targeted therapy has revolutionized the treatment strategy for HCC, offering survival hope to advanced-stage patients. Targeted therapy can not only extend the survival of patients with advanced disease when used alone, but also achieves satisfactory therapeutic effects when combined with other treatments. Sorafenib and lenvatinib are the sole two approved first-line targeted therapeutic drugs. Lenvatinib was officially approved by the FDA in 2019 as a first-line targeted drug, exhibiting superior overall survival efficacy compared to sorafenib. Consequently, lenvatinib, as the preferred first-line targeted therapy at present, occupies an indispensable position in prolonging the survival of advanced HCC patients. Unfortunately, the increasing prevalence of lenvatinib resistance has significantly hindered its clinical application, preventing a substantial proportion of patients from fully benefiting from this frontline medication. Therefore, elucidating the underlying mechanisms of resistance is crucial to tackle lenvatinib resistance and facilitate research aimed at reversing resistance. This review summarizes the lenvatinib resistance mechanisms focusing on HCC cell plasticity, abnormal transport processes, abnormal cell proliferation signaling pathways, escaped programmed cell death, and enhanced cancer cell metabolism.