Harnessing adrenergic receptor pathways in gliomas: from tumor biology to targeted therapies

Brain tumor biology, characterized by aberrant tumorigenesis, relentless invasiveness and a dynamic tumor microenvironment, drives the aggressive progression of gliomas, necessitating novel therapeutic strategies. Gliomas, aggressive brain tumors with dismal survival rates, pose a significant therapeutic challenge despite multimodal treatments. Adrenergic receptors (ARs), including α-and β-subtypes, are increasingly recognized as pivotal drivers of glioma biology, orchestrating tumorigenesis through dysregulated signaling pathways like cAMP/PKA, MAPK and PI3K/AKT. These pathways fuel proliferation, invasion and angiogenesis, while AR crosstalk with receptors such as EGFR and P2Y12 modulates the tumor microenvironment. This review integrates cutting-edge insights into ARs' multifaceted roles in glioma progression, emphasizing their potential as diagnostic biomarkers and therapeutic targets. We explore innovative strategies, including β-AR blockade with agents like propranolol and synergistic receptor-targeted therapies, to overcome treatment resistance and enhance patient outcomes. By decoding AR signaling in gliomas, this work highlights new avenues for precision medicine in neuro-oncology.