Li Zi-Zhan, Zhou Kan, Wu Jinmei, Cao Lei-Ming, Wang Guang-Rui, Luo Han-Yue, Liu Bing, Bu Lin-Lin
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China.
National Key Laboratory of Agricultural Microbiology, College of Chemistry, College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070, Hubei, China.
Research (Wash D C). 2025 Sep 9;8:0880. doi: 10.34133/research.0880. eCollection 2025.
Cancer persists as one of the most formidable global public health crises and socioeconomic burdens of our era, compelling the scientific community to develop innovative and diversified therapeutic modalities to revolutionize clinical management and enhance patient outcomes. The recent seminal discovery by Swamynathan et al. has unveiled menadione, a vitamin K precursor, as a potent inducer of triaptosis-a novel regulated cell death pathway mediated through the oxidative modulation of phosphatidylinositol 3-kinase PIK3C3/VPS34. This mechanistically distinct cell death paradigm, characterized by its intimate association with endosomal dysfunction and oxidative stress-induced cellular catastrophe, has demonstrated remarkable therapeutic efficacy in preclinical prostate cancer models, outperforming conventional therapeutic regimens and emerging as a potential paradigm-shifting strategy in oncology. This comprehensive review provides a critical synthesis of the triaptosis discovery landscape, elucidating its molecular intricacies and pathophysiological implications. We systematically examine the multifaceted roles of endosomal biology in oncogenesis and tumor progression, while offering a nuanced perspective on redox homeostasis in malignant cells and the therapeutic potential of oxidative stress modulation. Furthermore, we address the inherent dichotomy of oxidative stress induction in cancer therapy, balancing its therapeutic promise against potential adverse effects. Looking toward the horizon of cancer research, we explore transformative therapeutic strategies leveraging triaptosis induction and its potential applications beyond oncology, aiming to catalyze a new era of precision medicine that ultimately enhances patient survival and quality of life.
癌症仍然是我们这个时代最严峻的全球公共卫生危机和社会经济负担之一，促使科学界开发创新和多样化的治疗方式，以彻底改变临床管理并改善患者预后。Swamynathan等人最近的重大发现揭示了维生素K前体甲萘醌是三重凋亡的强效诱导剂，三重凋亡是一种通过磷脂酰肌醇3激酶PIK3C3/VPS34的氧化调节介导的新型程序性细胞死亡途径。这种机制上截然不同的细胞死亡模式，其特点是与内体功能障碍和氧化应激诱导的细胞灾难密切相关，在临床前前列腺癌模型中已显示出显著的治疗效果，优于传统治疗方案，并成为肿瘤学中一种潜在的范式转变策略。这篇全面的综述对三重凋亡的发现情况进行了批判性总结，阐明了其分子复杂性和病理生理意义。我们系统地研究了内体生物学在肿瘤发生和肿瘤进展中的多方面作用，同时对恶性细胞中的氧化还原稳态及其氧化应激调节的治疗潜力提供了细致入微的观点。此外，我们探讨了癌症治疗中氧化应激诱导的内在二分法，平衡其治疗前景与潜在的不良反应。展望癌症研究的未来，我们探索利用三重凋亡诱导的变革性治疗策略及其在肿瘤学之外的潜在应用，旨在开创一个精准医学的新时代，最终提高患者的生存率和生活质量。
