老药新用，双管齐下！湘雅医院最新Cell子刊：增强铁死亡，促进癌症免疫治疗

Core Viewpoint - Immunotherapy, particularly immune checkpoint blockade (ICB), presents transformative potential for treating various malignancies, but challenges such as acquired resistance and immune-related adverse events (irAEs) persist, necessitating a dual approach to address both thromboembolic risks and treatment resistance [2][5]. Group 1: Research Findings - A study published in Cell Reports Medicine indicates that the antiplatelet drug Vorapaxar enhances mitochondria-associated ferroptosis, thereby improving cancer immunotherapy outcomes by targeting the FOXO1/HMOX1 axis [3][6]. - Vorapaxar, approved by the FDA in 2014, reversibly inhibits the PAR-1 receptor on platelets, blocking thrombin-mediated platelet activation, which is crucial for antithrombotic therapy [6]. - The study confirms that Vorapaxar binds to FOXO1, inhibiting its phosphorylation and promoting its nuclear translocation, leading to increased expression of heme oxygenase-1 (HMOX1) and subsequent mitochondrial iron overload and ferroptosis [6]. Group 2: Clinical Implications - Vorapaxar has been shown to enhance immune therapy-induced tumor ferroptosis and antitumor immunity in various melanoma mouse models, suggesting its potential as a powerful adjunct in immunotherapy [6][8]. - High co-expression of FOXO1/HMOX1 is associated with improved responses to immunotherapy and prolonged progression-free survival, indicating a promising biomarker for treatment efficacy [6][8]. - Overall, Vorapaxar is positioned as a dual-benefit solution for cancer patients requiring both thrombolytic and immunotherapeutic interventions, addressing the dual challenges of thromboembolism and treatment resistance [8].