Ferroptosis-inducing therapy has emerged as a promising strategy in cancer treatment, especially for tumors resistant to therapies that induce conventional cell death, such as apoptosis [1]. Mechanistically, normal metabolic activities can generate phospholipid peroxides on cellular membranes, which, if unchecked, compromise membrane integrity and induce ferroptotic cell death [2, 3]. Therefore, regulating cellular lipid composition to control the levels of peroxidation-prone phospholipids is critical for determining cellular susceptibility to ferroptosis. A recent study by Li et al. in Nature Cell Biology identified lysophosphatidylcholine acyltransferase 1 (LPCAT1) as a key factor in driving ferroptosis resistance by enhancing membrane phospholipid saturation through the Lands cycle [4]. They further revealed that inhibiting LPCAT1, in combination with ferroptosis inducers, synergistically triggered ferroptosis and suppressed tumor growth in preclinical models, highlighting LPCAT1 as a valuable target for ferroptosis-inducing therapies in cancer treatment [4].

Cellular membranes are dynamic structures composed of diverse lipids essential for maintaining cell integrity and functionality. Phospholipids, serving as the main structural elements within these membranes, consist of a glycerol backbone linked to a polar head group at the sn-3 position and two fatty acid chains at the sn-1 and sn-2 positions. Typically, the fatty acid at the sn-1 position is either a saturated fatty acid (SFA, lacking double bonds) or a monounsaturated fatty acid (MUFA, with one double bond), whereas the fatty acid at the sn-2 position can be SFA, MUFA, or polyunsaturated fatty acid (PUFA, which contains multiple double bonds) [5].

铁死亡诱导疗法已成为癌症治疗中一种有前途的策略，特别是对于对诱导传统细胞死亡（例如细胞凋亡）疗法具有抵抗力的肿瘤[1]。从机制上讲，正常的代谢活动会在细胞膜上产生磷脂过氧化物，如果不加以控制，会损害膜的完整性并诱导铁死亡[2, 3]。因此，调节细胞脂质组成以控制易过氧化的磷脂水平对于确定细胞对铁死亡的易感性至关重要。李等人最近的一项研究。在《自然细胞生物学》中，将溶血磷脂酰胆碱酰基转移酶 1 (LPCAT1) 确定为通过 Lands 循环增强膜磷脂饱和度来驱动铁死亡抵抗的关键因素 [4]。他们进一步揭示，在临床前模型中，抑制 LPCAT1 与铁死亡诱导剂相结合，可以协同触发铁死亡并抑制肿瘤生长，强调 LPCAT1 作为癌症治疗中铁死亡诱导疗法的一个有价值的靶点 [4]。

细胞膜是由维持细胞完整性和功能所必需的多种脂质组成的动态结构。磷脂作为这些膜内的主要结构元素，由连接到 sn-3 位极性头基的甘油主链和 sn-1 和 sn-2 位两条脂肪酸链组成。通常，sn-1 位的脂肪酸是饱和脂肪酸（SFA，缺乏双键）或单不饱和脂肪酸（MUFA，有一个双键），而 sn-2 位的脂肪酸可以是SFA、MUFA 或多不饱和脂肪酸（PUFA，含有多个双键）[5]。