Radioresistance in Glioblastoma and the Development of Radiosensitizers
Abstract
:Simple Summary
Abstract
1. Introduction
2. History and Current Status of GBM Detection and Imaging Techniques
3. Treatment Options for GBM/History of GBM Treatment
4. Current Status of Radiation Treatment in GBM and Emergence of Radioresistance
5. Mechanisms of GBM Radioresistance
5.1. Tumor Microenvironment
5.2. Hypoxia
5.3. Metabolic Alteration
5.4. Glioma Stem Cells
5.5. GBM Tumor Heterogeneity
5.6. MicroRNAs
5.7. Cell Cycle, DNA Repair and Other Signaling Pathways
6. Radiosensitizers in GBM and Other Cancer Treatment
7. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Name of the Radiosensitizers | Effect | References |
---|---|---|
Gemcitabine | Initiates DNA damage by incorporating gemcitabine triphosphate, an active metabolite of gemcitabine, instead of nucleotide deoxycytidine triphosphate (dCTP) | [272,276] |
Gö6976 | Protein kinase inhibitor | [277] |
Talazoparib | PARP inhibitor | [278] |
MEK162 | MAPK inhibitor | [279] |
Erlotinib | EGFR inhibitor | [280] |
Everolimus | mTOR inhibitor | [281] |
Valproate | HDAC | [282] |
Vorinostat | HDAC inhibitor | [283] |
Vandetanib | VEGFR2 inhibitor | [284] |
Enzastaurin | Protein Kinase C (PKC) inhibitor | [285] |
Talampanel | alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist | [286] |
TMZ | Alkylates/methylates DNA at N-7 or O-6 positions of guanine residue | [287] |
Bortezomib | Proteasome inhibitor | [288] |
Resveratrol | STAT3 inhibitor | [218] |
Veliparib | PARP inhibitor | [289] |
Adavosertib | WEE1 inhibitor | [290] |
Chloroquine | Inhibits autophagy and induces apoptosis | [291,292] |
Ascorbate | Pro-oxidant | [293] |
RRx-001 | Macrophage-stimulating agent | [294] |
Motexafin gadolinium | Inhibits thioredoxin reductase and ribonucleotide reductase | [295] |
NVX-108 | Carries oxygen to the hypoxic tissue | [296] |
Trans sodium crocetinate | Enhances oxygen levels in hypoxic tissue | [297] |
Arsenic trioxide | Activates apoptosis and autophagy | [298,299,300] |
Sulfasalazine | Inhibits cystine uptake | [301] |
Palbociclib | CDK inhibitor | [302] |
KU - 55933 | ATM inhibitor | [303] |
AZD1390 | ATM inhibitor | [304] |
Study ID | Phase | Diagnosis | Treatment | Outcomes |
---|---|---|---|---|
NCT01752491 | I | GBM | Ascorbate, TMZ, and radiotherapy | No dose-limiting toxicities [293] |
NCT01465347 | I & II | GBM | Trans sodium crocetinate (TSC), TMZ, and radiotherapy | No adverse effects. Suggests radiotherapy and TSC combination is beneficial for GBM treatment. No significant difference in overall survival [297]. |
NCT00185861 | I | Recurrent malignant glioma | Arsenic trioxide (ATO) and stereotactic radiotherapy | ATO and fractionated stereotactic radiotherapy is well-tolerated [298] |
NCT04205357 | I | Recurrent GBM | Sulfasalazine and stereotactic radiotherapy | Study ongoing, recruiting patients |
NCT02871843 | I | GBM, oligodendroglioma, anaplastic oligodendroglioma | RRx-001, TMZ, and radiotherapy | Study ongoing |
NCT00302159 | II | High-grade gliomas | Valproic acid (VPA), TMZ, and radiotherapy | No adverse effects; VPA in combination with TMZ and radiotherapy can improve outcome [282] |
NCT00305864 | I & II | GBM | Motexafin gadolinium, TMZ, and radiotherapy | No adverse effects; no significant improvement in overall survival [295] |
NCT03862430 | II | GBM | NVX-108, TMZ, and radiotherapy | Study ongoing |
NCT03672721 | I & II | GBM | Carboplatin and radiotherapy | Study ongoing |
NCT02378532 | I | GBM | Chloroquine, TMZ, and radiotherapy | No adverse effects reported [305] |
NCT02432417 | II | GBM | Chloroquine, TMZ, and radiotherapy | Study ongoing |
NCT01849146 | I | Newly diagnosed and recurrent GBM | Adavosertib, TMZ, and radiotherapy | Study ongoing |
NCT03423628 | I | GBM | AZD1390 and Radiotherapy | Study ongoing |
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Ali, M.Y.; Oliva, C.R.; Noman, A.S.M.; Allen, B.G.; Goswami, P.C.; Zakharia, Y.; Monga, V.; Spitz, D.R.; Buatti, J.M.; Griguer, C.E. Radioresistance in Glioblastoma and the Development of Radiosensitizers. Cancers 2020, 12, 2511. https://doi.org/10.3390/cancers12092511
Ali MY, Oliva CR, Noman ASM, Allen BG, Goswami PC, Zakharia Y, Monga V, Spitz DR, Buatti JM, Griguer CE. Radioresistance in Glioblastoma and the Development of Radiosensitizers. Cancers. 2020; 12(9):2511. https://doi.org/10.3390/cancers12092511
Chicago/Turabian StyleAli, Md Yousuf, Claudia R. Oliva, Abu Shadat M. Noman, Bryan G. Allen, Prabhat C. Goswami, Yousef Zakharia, Varun Monga, Douglas R. Spitz, John M. Buatti, and Corinne E. Griguer. 2020. "Radioresistance in Glioblastoma and the Development of Radiosensitizers" Cancers 12, no. 9: 2511. https://doi.org/10.3390/cancers12092511