Cancer cells show altered antioxidant defense systems, dysregulated redox signaling, and increased generation of reactive oxygen species (ROS). Targeting cancer cells through ROS-mediated mechanisms has emerged as a significant therapeutic strategy due to its implications in cancer progression, survival, and resistance. Extensive research has focused on selective generation of H2O2in cancer cells for selective cancer cell killing by employing various strategies such as metal-based prodrugs, photodynamic therapy, enzyme-based systems, nano-particle mediated approaches, chemical modulators, and combination therapies. Many of these H2O2-amplifying approaches have demonstrated promising anticancer effects and selectivity in preclinical investigations. They selectively induce cytotoxicity in cancer cells while sparing normal cells, sensitize resistant cells, and modulate the tumor microenvironment. However, challenges remain in achieving selectivity, addressing tumor heterogeneity, ensuring efficient delivery, and managing safety and toxicity. To address those issues, H2O2-generating agents have been combined with other treatments leading to optimized combination therapies. This review focuses on various chemical agents/approaches that kill cancer cells via H2O2-mediated mechanisms. Different categories of compounds that selectively generate H2O2in cancer cells are summarized, their underlying mechanisms and function are elucidated, preclinical and clinical studies as well as recent advancements are discussed, and their prospects as targeted therapeutic agents and their therapeutic utility in combination with other treatments are explored. By understanding the potential of these compounds, researchers can pave the way for the development of effective and personalized cancer treatments.
癌细胞表现出抗氧化防御系统改变、氧化还原信号失调以及活性氧（ROS）生成增加的特点。通过ROS介导机制靶向癌细胞已成为重要的治疗策略，因其在癌症进展、存活及耐药性中具有关键作用。当前研究聚焦于利用多种策略在癌细胞中选择性生成过氧化氢（H₂O₂）以实现特异性杀伤，包括金属前药、光动力疗法、酶基系统、纳米颗粒介导方法、化学调节剂及联合疗法等。大量临床前研究表明，这些H₂O₂扩增策略展现出良好的抗癌效果与选择性：能特异性诱导癌细胞毒性而不损伤正常细胞，增敏耐药细胞，并调节肿瘤微环境。然而，该领域仍面临选择性提升、肿瘤异质性应对、递送效率优化及安全性控制等挑战。为解决这些问题，H₂O₂生成剂已与其他治疗手段结合形成优化联合方案。本综述系统阐述通过H₂O₂介导机制杀伤癌细胞的各类化学制剂及方法，归纳了在癌细胞中选择性生成H₂O₂的不同化合物类别，阐明其作用机制与功能，探讨临床前与临床研究进展，并展望其作为靶向治疗剂的潜力及联合治疗应用前景。通过深入理解这些化合物的潜力，研究者可为开发高效个性化癌症治疗方案开辟新路径。
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