Advances in the role of astrocytes in glioma progression and therapy.

Glioblastoma is the most common malignant primary intracranial tumor, characterized by high invasiveness, rapid progression, and poor sensitivity to radiotherapy and chemotherapy. Given the limited efficacy of current treatments, novel therapeutic strategies are urgently needed. Astrocytes play pivotal roles in glioma initiation and progression by promoting tumor proliferation, invasion, therapeutic resistance, and immune evasion. Reactive astrocytes are increasingly recognized as dynamic, heterogeneous cell states rather than fixed subtypes. This review discusses representative astrocyte programs linked to immune modulation, tumor support, and therapy response, including TRAIL-associated, STAT3/CHI3L1-related, and PDGFR-β-associated phenotypes. Furthermore, the study describes emerging astrocyte-targeted strategies, such as blocking pro-tumor cytokine signaling, disrupting astrocyte-glioma communication, inhibiting extracellular vesicle transfer, and modulating immunosuppressive astrocyte states. Targeting tumor-associated astrocytes may offer new strategies to counter glioblastoma progression, immune escape, and therapeutic resistance.