期刊：DRUG RESISTANCE UPDATES

作者列表：Zhongyan Zhang, Qi Zhou, Zhenchong Li, Fuxin Huang, Ke Mo, Cheng Shen, Xing Niu, Baohua Hou, Chuanzhao Zhang, Shanzhou Huang

发表时间：2025-2-28

影响因子：21.7

DOI:10.1016/j.drup.2025.101224

主要研究成果：Abstract

Aims

Emerging resistance to Lenvatinib, which is used as a first-line agent for the treatment of advanced hepatocellular carcinoma (HCC), is still a concern. The aim of this study was to determine core factors of Lenvatinib resistance (LR) and their underlying molecular mechanisms.

Methods

CRISPR screening in HCC cells was conducted, which identified E3 ubiquitin ligase deltex 2 (DTX2) as a core LR-related gene. In vivo and in vitro models were used to clarify the function of DTX2 on LR and ferroptosis. The upstream regulators and downstream effectors of DTX2 were identified, revealing its complex regulatory network.