铁死亡抗癌新突破！背靠背两篇Nature：靶向FSP1，促进癌症铁死亡

Core Viewpoint - Ferroptosis is a newly discovered iron-dependent form of programmed cell death that plays a significant role in cancer and other diseases, with potential implications for immunotherapy and radiotherapy [1][2]. Group 1: Ferroptosis Mechanism and Importance - Ferroptosis is characterized by the accumulation of peroxidized lipids and is distinct from other forms of cell death [1]. - Key defense mechanisms against ferroptosis include GPX4, which inhibits ferroptosis by catalyzing peroxidized lipids, and FSP1, which promotes cancer cell resistance to ferroptosis through the antioxidant form of coenzyme Q10 [1]. Group 2: Research Findings on Lung Cancer - A study published on November 5, 2025, demonstrated that targeting FSP1 triggers ferroptosis in lung cancer, indicating that lung cancer is highly sensitive to ferroptosis [4][6]. - The research showed that the knockout of the FSP1 gene in tumors led to increased lipid peroxidation and significant tumor suppression, highlighting the protective role of FSP1 in vivo [6][7]. - FSP1 expression is prognostic for disease progression and survival in lung adenocarcinoma patients, suggesting its potential as a therapeutic target [7][9]. Group 3: FSP1 in Melanoma - Another study indicated that FSP1 targeting in the lymph node environment could effectively inhibit the progression of metastatic melanoma [10][16]. - The research found that metastatic melanoma cells showed decreased expression of GCLC and reduced levels of GSH in the hypoxic lymphatic microenvironment, leading to increased reliance on FSP1 [13][16]. - Selective FSP1 inhibitors demonstrated significant efficacy in suppressing melanoma growth in lymph nodes, emphasizing the specific dependency of melanoma cells on FSP1 in that microenvironment [13][16].