如何有效诱导肿瘤细胞死亡一直是癌症治疗的热点，铁死亡作为一种新的细胞死亡形式，其诱导剂的应用有望为肿瘤治疗提供新的思路。本课题拟探索利用铁死亡治疗肝癌的新策略，并在此基础上探讨如何增强铁死亡耐药细胞株的治疗效果及其分子机制。本研究前期发现铁死亡诱导剂引起肝癌细胞发生特异性的铁死亡，并且能够在体内和体外抑制肝癌的生长，然而，一些肝癌细胞对其杀伤作用不敏感。基于以上结果，我们通过CRISPR-Cas9功能基因组学筛查技术，发现抑制CSK（C-terminal Src kinase）可显著提高肝癌细胞对铁死亡的敏感性。在后续研究中，我们将探讨CSK在肿瘤细胞铁死亡抵抗中的作用及分子机制，并系统研究铁死亡诱导剂联合CSK抑制剂对肝癌的协同抑制作用，同时在动物水平探索该联合用药的可行性。本研究有望为肝癌治疗提供新的实验依据。

How to effectively induce tumor cell death has been a hot topic in cancer treatment. Ferroptosis, as a new form of regulated cell death, is expected to provide a new method for cancer treatment. Here, we attempt to identify novel treatment strategy by inducing ferroptosis in hepatocellular carcinoma (HCC). Furthermore, we will explore the new approach to enhance the sensitivity of ferroptosis resistant cell line and its molecular mechanism. In previous experiments, we found that ferroptosis inducer caused specific ferroptotic cell death in HCC cells，and could inhibit the growth of HCC in vitro and in vivo. However, some HCC cells were insensitive to ferroptosis inducer. By functional genetic screens based on CRISPR-Cas9 technology, we found that inhibition of CSK（C-terminal Src kinase）significantly increased the sensitivity of cells to ferroptosis. In the further study, we are planning to explore the role and molecular mechanism of CSK in ferroptotic cell death resistance, systematically study the synergistic inhibitory effect of ferroptosis inducer combined with CSK inhibitor in HCC. In addition, we will investigate the feasibility of this drug combination by using xenografts models. This study may provide a novel and promising therapeutic approach to the treatment of HCC.