浙大校友一作Nature论文：揭开癌细胞抵抗铁死亡的关键机制

Core Viewpoint - Ferroptosis is a newly discovered iron-dependent form of programmed cell death that plays a significant role in tumor development and resistance to cancer therapies, highlighting the need for further research into its mechanisms to enhance cancer treatment strategies [1][2]. Group 1: Mechanism of Ferroptosis - Ferroptosis is characterized by the accumulation of peroxidized lipids, and it differs significantly from other forms of programmed cell death [1]. - Cells have various defense mechanisms against ferroptosis, such as GPX4, which inhibits ferroptosis by catalyzing peroxidized lipids using glutathione [1]. - FSP1 promotes cancer cell resistance to ferroptosis by generating the antioxidant form of coenzyme Q10 [1]. Group 2: Role in Cancer Treatment - Recent studies indicate that ferroptosis plays a crucial role in the efficacy of immunotherapy and radiotherapy, suggesting that understanding tumor resistance mechanisms could expand current cancer treatment options [2]. - The research published in Nature identifies glycosaminoglycan-driven lipoprotein uptake as a key mechanism for cancer cells to resist ferroptosis, indicating a potential new target for cancer therapy [3]. Group 3: Lipoprotein Uptake and Cancer Growth - The study reveals that lipoprotein uptake is a critical determinant of cancer cell sensitivity to ferroptosis, with supplementation of lipoproteins effectively inhibiting ferroptosis across various cancer types [6]. - Cancer cells utilize a pathway dependent on sulfated glycosaminoglycans to uptake lipoproteins, and disrupting this pathway increases sensitivity to ferroptosis and inhibits tumor growth in mice [7][11]. - Elevated levels of sulfated glycosaminoglycans and lipoprotein-derived α-tocopherol were observed in clear cell renal carcinoma compared to normal kidney tissue, further supporting the role of lipoprotein uptake in cancer progression [10].