4.7 Review

Hypoxia: The Cornerstone of Glioblastoma

期刊

出版社

MDPI
DOI: 10.3390/ijms222212608

关键词

glioblastoma; hypoxia; HIF-1; HIF-1 inhibitors

资金

  1. Instituto de la Salud Carlos III [CM19/00068]

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Glioblastoma is the most aggressive form of brain tumor in adults, with hypoxia-induced factor 1 (HIF-1) serving as an important driver of tumor progression by promoting angiogenesis, immunosuppression, and metabolic reprogramming. HIF-1 is not only regulated by oxygen levels but also by various oncogenic signaling pathways, and inhibiting the hypoxia pathway could be a crucial treatment alternative for GB patients.
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-1 alpha is a transcription factor regulated by the presence or absence of O-2. 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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