Balanced Duality: H2O2-Based Therapy in Cancer and Its Protective Effects on Non-Malignant Tissues
Abstract
:1. Introduction
2. H2O2 as a Signaling Molecule
3. H2O2 in Cancer: A Sliding Scale
4. Targeting H2O2 in Cancer: Enhancing Conventional Therapy and Minimizing Its Normal Tissue Toxicities
4.1. Pharmacological Ascorbate
Trial | Disease | Therapy | Outcomes | Reference |
---|---|---|---|---|
NCT02344355 Phase 2 | GBM | P-AscH− with radiation and temozolomide. | Increased overall survival (19.6 months) compared to 14.6 months in historical controls. | [116] |
NCT00228319 Phase 1/2a | Ovarian cancer | P-AscH− with carboplatin and paclitaxel. |
| [117] |
NCT01049880 Phase 1 | Pancreatic cancer | P-AscH− with gemcitabine. |
| [118] |
NCT00954525 Phase 1 | Pancreatic cancer | P-AscH− with gemcitabine and erlotinib. | P-AscH− was well tolerated. | [119] |
NCT01364805 Phase 1/2a | Pancreatic cancer | P-AscH− with gemcitabine. | Trend toward increasing overall survival. | [120] |
NCT02905578 Phase 2 | Pancreatic cancer | P-AscH− with gemcitabine. | Ongoing trial. | - |
NCT02420314 Phase 2 | NSCLC | P-AscH− with carboplatin and paclitaxel. |
| [121] |
NCT03146962 Phase 3 | Colorectal cancer | P-AscH− with FOLFOX ± Bevacizumab. | Increased progression-free survival to 9.2 months vs. 7.8 in the control group. This effect was limited to patients with RAS-mutant tumors. | [131] |
NCT01080352 Phase 2 | Prostate cancer | P-AscH− | No benefits to the use of P-AscH- as a treatment. | [132] |
NCT02516670 Phase 2 | Prostate cancer | P-AscH− with docetaxel. | No benefits from the addition of P-AscH- to the treatment regimen. | [133] |
NCT03468075 Phase 2 | Soft tissue sarcoma | P-AscH− with gemcitabine. | Terminated. | - |
NCT03508726 Phase 1b/2 | Soft tissue sarcoma | P-AscH− with radiation. | Completed. | - |
NCT04900792 Phase 1 | GBM | P-AscH− with ferumoxytol, radiation, and temozolomide. | Ongoing trial. | - |
4.2. Superoxide Dismutase Mimetics
Trial | Disease | Therapy | Outcomes | Reference |
---|---|---|---|---|
NCT02990468 Phase 1/2 | Head and neck cancer | MnBuOE with radiation and cisplatin | Ongoing trial. | - |
NCT02655601 Phase 2 | High-grade glioma | MnBuOE with radiation and temozolomide | Ongoing trial. | - |
NCT03386500 Phase 1 | Anal cancer | MnBuOE with radiation, 5FU, and mitomycin | Ongoing trial. | - |
NCT05254327 Phase 2 | Rectal cancer | MnBuOE with radiation and chemotherapy (oxaliplatin, leucovorin, fluorouracil, capecitabine) | Ongoing trial. | - |
NCT01921426 Phase 1b/2a | Head and neck cancer | AVA with radiation and cisplatin | Reduction in the incidence of severe radiation-induced oral mucositis by 50% (relative to historical controls). | [183] |
NCT02508389 Phase 2b | Head and neck cancer | AVA with radiation and cisplatin |
| [180,182] |
NCT03689712 Phase 3 | Head and neck cancer | AVA with radiation and cisplatin |
| [181] |
5. Concluding Remarks
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Damage Mechanism | Outcome | Reference |
---|---|---|
Mitochondrial Dysfunction | Decreased ATP synthesis, impaired mitochondrial function. | [9] |
Fenton Chemistry | DNA, lipid, and protein damage. | [10] |
Protein Modification | Irreversible protein oxidation and fragmentation, mitochondrial dysfunction, hyperactivation or inactivation of essential proteins (e.g., kinases). | [11,12,13] |
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Zaher, A.; Petronek, M.S.; Allen, B.G.; Mapuskar, K.A. Balanced Duality: H2O2-Based Therapy in Cancer and Its Protective Effects on Non-Malignant Tissues. Int. J. Mol. Sci. 2024, 25, 8885. https://doi.org/10.3390/ijms25168885
Zaher A, Petronek MS, Allen BG, Mapuskar KA. Balanced Duality: H2O2-Based Therapy in Cancer and Its Protective Effects on Non-Malignant Tissues. International Journal of Molecular Sciences. 2024; 25(16):8885. https://doi.org/10.3390/ijms25168885
Chicago/Turabian StyleZaher, Amira, Michael S. Petronek, Bryan G. Allen, and Kranti A. Mapuskar. 2024. "Balanced Duality: H2O2-Based Therapy in Cancer and Its Protective Effects on Non-Malignant Tissues" International Journal of Molecular Sciences 25, no. 16: 8885. https://doi.org/10.3390/ijms25168885