Regarding P2X4R, the mechanism of action in GBM is activation of P2X4R leading to increased brain-derived neurotrophic factor (BDNF)/Trk receptor tyrosine kinase (TrkB) signaling which work in concert to upregulate activating transcription factor 4 (ATF4), a key promoter of cancer cell survival in hypoxic environments (Trang et al., 2009; Singleton and Harris, 2012; Huo and Chen, 2019). This evidence concerns the gene ATF4 and glioblastoma.