Department of Radiation Oncology, The University of Iowa, Iowa City, IA 52242, USA.
Int J Mol Sci. 2024 Aug 15;25(16):8885. doi: 10.3390/ijms25168885.
Conventional cancer therapy strategies, although centered around killing tumor cells, often lead to severe side effects on surrounding normal tissues, thus compromising the chronic quality of life in cancer survivors. Hydrogen peroxide (HO) is a secondary signaling molecule that has an array of functions in both tumor and normal cells, including the promotion of cell survival pathways and immune cell modulation in the tumor microenvironment. HO is a reactive oxygen species (ROS) crucial in cellular homeostasis and signaling (at concentrations maintained under nM levels), with increased steady-state levels in tumors relative to their normal tissue counterparts. Increased steady-state levels of HO in tumor cells, make them vulnerable to oxidative stress and ultimately, cell death. Recently, HO-producing therapies-namely, pharmacological ascorbate and superoxide dismutase mimetics-have emerged as compelling complementary treatment strategies in cancer. Both pharmacological ascorbate and superoxide dismutase mimetics can generate excess HO to overwhelm the impaired HO removal capacity of cancer cells. This review presents an overview of HO metabolism in the physiological and malignant states, in addition to discussing the anti-tumor and normal tissue-sparing mechanism(s) of, and clinical evidence for, two HO-based therapies, pharmacological ascorbate and superoxide dismutase mimetics.
传统的癌症治疗策略虽然以杀死肿瘤细胞为中心，但往往会对周围正常组织产生严重的副作用，从而影响癌症幸存者的慢性生活质量。过氧化氢（HO）是一种二级信号分子，在肿瘤细胞和正常细胞中具有多种功能，包括促进细胞存活途径和肿瘤微环境中的免疫细胞调节。HO 是一种活性氧（ROS），在细胞内稳态和信号转导中起着至关重要的作用（在维持在纳摩尔水平的浓度下），与正常组织相比，肿瘤中的稳态水平增加。肿瘤细胞中 HO 的稳态水平增加，使它们容易受到氧化应激的影响，最终导致细胞死亡。最近，产生 HO 的治疗方法——即药理学抗坏血酸和超氧化物歧化酶模拟物——已成为癌症治疗中引人注目的补充治疗策略。药理学抗坏血酸和超氧化物歧化酶模拟物都可以产生过量的 HO 来克服肿瘤细胞受损的 HO 清除能力。本综述介绍了 HO 在生理和恶性状态下的代谢，此外还讨论了两种基于 HO 的治疗方法——药理学抗坏血酸和超氧化物歧化酶模拟物的抗肿瘤和正常组织保护机制及其临床证据。
