Targeting ferroptosis in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a common malignant tumor with complex survival mechanism and drug resistance, resulting in cancer-related high mortality in the world. Ferroptosis represents a form of regulated cell death, typically distinguished by iron-dependent lipid peroxidation. Cancer cells often employ antioxidant defenses to evade the harmful effects of excess iron. Recent research has proposed that directing interventions towards ferroptosis could serve as an effective strategy in curbing the proliferation and invasion of HCC. Immunotherapy has made some preliminary progress in the remodeling of immune microenvironment, but it has not completely inhibited HCC growth, invasion and drug resistance. Furthermore, ferroptosis is widely observed in the formation of immune microenvironment of HCC and mediates the response of many targeted drugs and immunotherapy. Clarifying the role of ferroptosis in these complex processes is expected to provide a new prospect for HCC treatment. In this review, we outline the mechanisms by which HCC develops invasiveness and drug resistance by evading iron-dependent death, and paint a comprehensive landscape of ferroptosis in different cell types in the HCC immune microenvironment.