1. Generation of Hydrogen Peroxide in Cancer Cells: Advancing Therapeutic Approaches for Cancer Treatment.
- Author
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Ali, Taufeeque, Li, Daniel, Ponnamperumage, Thilini Nimasha Fernando, Peterson, Alexis Kimberly, Pandey, Jatin, Fatima, Kulsum, Brzezinski, John, Jakusz, Julia Anna Rose, Gao, Hanlun, Koelsch, Gilbert Edward, Murugan, Dhivyashree Senthil, and Peng, Xiaohua
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PATIENT safety , *APOPTOSIS , *CELL physiology , *CELL lines , *REACTIVE oxygen species , *HYDROGEN peroxide , *MOLECULAR structure , *TUMORS - Abstract
Simple Summary: Cancer cells grow and divide so rapidly that they are literally engaged in a metabolic marathon—leading to the formation of high levels of reactive oxygen species (ROS). The altered redox balance in cancer cells offers therapeutic opportunities for targeting cancer. Some ROS-targeting strategies attempt to enhance ROS production to inflict lethal cell damage or trigger apoptosis, while other anticancer agents inhibit enzymes that are essential to maintain the redox potential of the cell. One type of ROS that shows potential to be utilized as a treatment mechanism is hydrogen peroxide (H2O2), which can be generated by numerous mechanisms, including metal-based prodrugs, photodynamic therapy, enzymes, nanoparticles, chemical modulators, and various combinations thereof. This review focuses on various chemical agents that induce H2O2-mediated cancer cell death, including their mechanism of function, preclinical and clinical studies, recent advancements, and potential applications as a new and exciting avenue for targeted and efficacious cancer treatment. 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 H2O2 in 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 H2O2 in 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. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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