P2X7R: A Critical Regulator and Potential Therapeutic Target for Glioma

ABSTRACT Glioma is the most common primary brain tumor, characterized by high invasiveness and poor prognosis. The purinergic ligand‐gated ion channel 7 receptor (P2X7R), an ion channel‐type purinergic receptor with adenosine triphosphate (ATP) as its ligand, is widely expressed in various tumor cells, including glioma. Moreover, it plays crucial biological functions in the progression of glioma. P2X7R promotes the proliferation, invasion, and metastasis of glioma by activating multiple signaling pathways, facilitating epithelial–mesenchymal transition (EMT), promoting the release of extracellular vesicles (EVs) and regulating the tumor microenvironment (TME) of glioma. However, the activation of P2X7R by high concentrations of ATP can induce cell necrosis or pyroptosis, exerting an anti‐glioma effect. The bidirectional nature of its functions may be related to differences in the subtypes of P2X7R, cell types, as well as the TME. P2X7R antagonists can inhibit its effect in glioma, while the expression of P2X7R can enhance the efficacy of radiotherapy and chemotherapy. In this review, the structure and function of P2X7R, its role in tumor, especially its mechanism of action in glioma, and its latent capacity value as a target for therapeutic of glioma were reviewed in detail.