Hypoxia: The Cornerstone of Glioblastoma
Abstract
:1. Introduction
2. What Is the Role of HIF-1?
3. HIF-1α Promotes GB Aggressiveness
4. Is HIF-1 the Main Promotor of Aggressiveness in Brain Tumors?
4.1. HIF-1 Expression Is Related to the Brain Tumor’s Grade
4.2. HIF-1α Participates in Signaling Pathways Involved in GB
5. Can We Block HIF-1 to Stop Tumor Progression?
6. Downregulating HIF-1 mRNA Expression
7. Inhibiting HIF-1 at the Protein Level
8. Promoting HIF-1 Degradation
9. Interfering in HIF-1 to HIF-1 HRE Binding
Drug Name | Mechanism of Action | Clinical Trial | Phase | Glioma Models | Ref |
---|---|---|---|---|---|
EZN-2208 | Downregulation of HIF-1 mRNA | NCT01251926 | Phase I | Yes | [115] |
Aminoflavone | Blockage of HIF-1α dimerization | NCT0101552 | Phase I | No | [104,105] |
EZN-2698 | Downregulation of HIF-1 mRNA | NCT01120288 | Phase I | Yes | [106,107] |
KC7F2 | Inhibition of HIF-1 translation | - | - | Yes | [110,111] |
103D5R | Inhibition of HIF-1 translation | - | - | Yes | [110,112] |
PX-478 | Downregulation of HIF-1 protein level | NCT00522652 | Phase I | ||
LBH589 | Downregulation of HIF-1 protein level | NCT01065467 NCT00859222 | Phase I Phase II | Yes | [72,73] |
Topotecan | Inhibition of HIF-1 protein synthesis | Approved for other cancer types | - | Yes | [114] |
OKN-007 | Downregulation of HIF-1 mRNA | NCT01672463 | Phase Ib | Yes | [108,109] |
Cardiac glycosides | Downregulation of HIF-1 protein synthesis | - | - | Yes | [77,78] |
Vorinostat | Degradation of the HIF-1 protein | Approved for other cancer treatments | - - | No | [118] |
Echinomycin | Blockage of HIF-1 DNA binding | Approved | - | Yes | [82] |
Acriflavine | Blockage of HIF-1 DNA binding | Antifungal approved drug | - | Yes | [83,84] |
Icaritin | Degradation of HIF-1α | NCT02496949 | Phase I | Yes | [124] |
KCN1 | Blockage of HIF-1 and coactivators p300/CBP | - | - | Yes | [129] |
Chetomin | Blockage of HIF-1 and coactivators p300/CBP | - | - | [85] |
10. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Domènech, M.; Hernández, A.; Plaja, A.; Martínez-Balibrea, E.; Balañà, C. Hypoxia: The Cornerstone of Glioblastoma. Int. J. Mol. Sci. 2021, 22, 12608. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222212608
Domènech M, Hernández A, Plaja A, Martínez-Balibrea E, Balañà C. Hypoxia: The Cornerstone of Glioblastoma. International Journal of Molecular Sciences. 2021; 22(22):12608. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222212608
Chicago/Turabian StyleDomènech, Marta, Ainhoa Hernández, Andrea Plaja, Eva Martínez-Balibrea, and Carmen Balañà. 2021. "Hypoxia: The Cornerstone of Glioblastoma" International Journal of Molecular Sciences 22, no. 22: 12608. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222212608