Hypoxia: The Cornerstone of Glioblastoma.
Int J Mol Sci
; 22(22)2021 Nov 22.
Article
em En
| MEDLINE
| ID: mdl-34830491
ABSTRACT
Glioblastoma is the most aggressive form of brain tumor in adults and is characterized by the presence of hypervascularization and necrosis, both caused by a hypoxic microenvironment. In this review, we highlight that hypoxia-induced factor 1 (HIF-1), the main factor activated by hypoxia, is an important driver of tumor progression in GB patients. HIF-1α is a transcription factor regulated by the presence or absence of O2. The expression of HIF-1 has been related to high-grade gliomas and aggressive tumor behavior. HIF-1 promotes tumor progression via the activation of angiogenesis, immunosuppression, and metabolic reprogramming, promoting cell invasion and survival. Moreover, in GB, HIF-1 is not solely modulated by oxygen but also by oncogenic signaling pathways, such as MAPK/ERK, p53, and PI3K/PTEN. Therefore, the inhibition of the hypoxia pathway could represent an important treatment alternative in a disease with very few therapy options. Here, we review the roles of HIF-1 in GB progression and the inhibitors that have been studied thus far, with the aim of shedding light on this devastating disease.
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Base de dados:
MEDLINE
Assunto principal:
Glioblastoma
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Microambiente Tumoral
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Neovascularização Patológica
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article