학술논문

Hypoxia: The Cornerstone of Glioblastoma
Document Type
article
Source
International Journal of Molecular Sciences, Vol 22, Iss 22, p 12608 (2021)
Subject
glioblastoma
hypoxia
HIF-1
HIF-1 inhibitors
Biology (General)
QH301-705.5
Chemistry
QD1-999
Language
English
ISSN
1422-0067
1661-6596
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.