EGFR Expression and Mechanism of Action in Glioblastoma

Epidermal growth factor receptor (EGFR) is frequently abnormal in about 60% of glioblastoma (GBM) patients, mainly manifested by gene amplification and EGFRvIII mutation, resulting in continuous activation of downstream signaling pathways , driving tumor cell proliferation, invasion, migration and stem cell characteristics maintenance. Multiple factors influence these pathways by regulating EGFR activity and stability through different mechanisms. In tumor microenvironment, secreted protein POSTN inhibits EGFR degradation, inflammatory factor PTX3 activates PI3K pathway, and JAK2/STAT3/STAT6 pathway induces M2-type macrophage polarization, which jointly promote GBM progression. In addition, EGFR signaling promotes tumor stem cells to differentiate into endothelial-like cells through RTK/PI3K/AKT pathway, forming vascular mimicry (VM) and accelerating tumor invasion and metastasis. Therapeutic strategies targeting EGFR include monoclonal antibodies and small molecule tyrosine kinase inhibitors, but have limited efficacy and resistance;CAR-T cell therapy targeting EGFR faces challenges such as tumor microenvironment inhibition. So further understanding of EGFR regulatory networks and drug resistance mechanisms is essential to optimize GBM therapy.