Fig. 2: Preclinical and clinical approaches to target tumor hypoxia in GBM.
From: Preclinical and clinical advances to overcome hypoxia in glioblastoma multiforme
The first-line therapy constitutes of a multimodal approach including surgery and chemoradiotherapy, yet GBM has been shown to exhibit resistance to such medical intervention. Although chronic or diffusion-limited hypoxia represents one of the pillars driving this aggressive behavior, it is overlooked in the diagnosis and treatment of GBM. Several preclinical and clinical approaches have been suggested as methods to reverse the effect of hypoxia on GBM response to conventional treatments. These include the inhibition of the hypoxia signaling pathway via HIFs, increasing the presence of oxygen within the tumor bulk or reoxygenation, targeting angiogenesis the main driver of tumor hypoxia, and reducing the cellular oxygen consumption via mitochondrial or cellular metabolism.
