Ferroptosis: From Basic Research to Clinical Therapeutics in Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) is one of the most common and highly heterogeneous malignancies worldwide. Despite the rapid development of multidisciplinary treatment and personalized precision medicine strategies, the overall survival of HCC patients remains poor. The limited survival benefit may be attributed to difficulty in early diagnosis, the high recurrence rate and high tumor heterogeneity. Ferroptosis, a novel mode of cell death driven by iron-dependent lipid peroxidation, has been implicated in the development and therapeutic response of various tumors, including HCC. In this review, we discuss the regulatory network of ferroptosis, describe the crosstalk between ferroptosis and HCCrelated signaling pathways, and elucidate the potential role of ferroptosis in various treatment modalities for HCC, such as systemic therapy, radiotherapy, immunotherapy, interventional therapy and nanotherapy, and applications in the diagnosis and prognosis of HCC, to provide a theoretical basis for the diagnosis and treatment of HCC to effectively improve the survival of HCC patients.

Pathogenesis of Hepatocellular Carcinoma: The Interplay of Apoptosis and Autophagy

“…Despite the all increasing importance of ferroptosis, there are no data on a possible interplay between ferroptosis, autophagy and apoptosis in HCC. The role of ferroptosis in HCC initiation and progression has been extensively reviewed [ 472 , 473 ].…”

Lenvatinib resistance mechanism and potential ways to conquer

“…Ferroptosis is different from other types of cell death, which containing cell apoptosis, necrosis, and autophagy ( Hassannia et al, 2019 ; Zhang et al, 2022b ). The characteristic of ferroptosis is that it’s highly accompanied by the iron-dependent accumulation of lethal lipid reactive oxygen species (ROS) ( Huang et al, 2023 ). The promotion of ferroptosis could significantly improve the killing ability of cancerous cells.…”

The Curative and Preventative Effects of Traditional Chinese Medicine on Ferroptosis of Hepatocellular Carcinoma

“…This holistic approach aims to address not only the tumor itself but also the overall well-being and constitution of the patient, thus offering a comprehensive and patient-centered strategy for managing this complex condition. Ferroptosis-inducing agents such as Erastin, 37 RSL3, 38 sorafenib, 39 sulfasalazine, and iron statins, along with modalities like ionizing radiation and cytokine-based approaches that have the potential to induce ferroptosis and inhibit tumor growth, present promising avenues within the realm of TCM for the treatment of HCC. Furthermore, an accumulating body of evidence underscores the potential of TCM in retarding the advancement of HCC by directing its therapeutic focus toward the ferroptosis pathway, as depicted in Figure 2.…”