Shanghai Institute of Cardiovascular Diseases, Department of Cardiology, Zhongshan Hospital Fudan University, Shanghai, China.
Department of Surgery, UT Southwestern Medical Center, Dallas, TX, 75390, USA.
Br J Cancer. 2023 Jan;128(2):190-205. doi: 10.1038/s41416-022-01998-x. Epub 2022 Oct 13.
Hepatocellular carcinoma is the most prevalent form of primary liver cancer with a multifactorial aetiology comprising genetic, environmental, and behavioural factors. Evading cell death is a defining hallmark of hepatocellular carcinoma, underpinning tumour growth, progression, and therapy resistance. Ferroptosis is a form of nonapoptotic cell death driven by an array of cellular events, including intracellular iron overload, free radical production, lipid peroxidation and activation of various cell death effectors, ultimately leading to rupture of the plasma membrane. Although induction of ferroptosis is an emerging strategy to suppress hepatocellular carcinoma, malignant cells manage to develop adaptive mechanisms, conferring resistance to ferroptosis and ferroptosis-inducing drugs. Herein, we aim at elucidating molecular mechanisms and signalling pathways involved in ferroptosis and offer our opinions on druggable targets and new therapeutic strategy in an attempt to restrain the growth and progression of hepatocellular carcinoma through induction of ferroptotic cell death.
肝细胞癌是原发性肝癌中最常见的一种，其病因具有多因素性，包括遗传、环境和行为因素。逃避细胞死亡是肝细胞癌的一个明确特征，为肿瘤的生长、进展和治疗耐药性提供了基础。铁死亡是一种由多种细胞事件驱动的非凋亡性细胞死亡形式，包括细胞内铁过载、自由基生成、脂质过氧化和各种细胞死亡效应器的激活，最终导致质膜破裂。尽管诱导铁死亡是抑制肝细胞癌的一种新兴策略，但恶性细胞设法发展出适应性机制，对铁死亡和铁死亡诱导药物产生耐药性。在此，我们旨在阐明铁死亡相关的分子机制和信号通路，并就潜在的治疗靶点和新的治疗策略提出我们的观点，试图通过诱导铁死亡性细胞死亡来抑制肝细胞癌的生长和进展。
