almonertinib + anlotinib + temozolomide

This is a combination therapy consisting of three small-molecule drugs: - **Almonertinib** is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), primarily used for the treatment of EGFR-mutant non-small cell lung cancer (NSCLC). It selectively inhibits both EGFR activating mutations and the T790M resistance mutation, blocking downstream signaling pathways involved in tumor proliferation and survival. - **Anlotinib** is a multi-targeted tyrosine kinase inhibitor that targets vascular endothelial growth factor receptors (VEGFR1/2/3), fibroblast growth factor receptors (FGFR1–4), platelet-derived growth factor receptors (PDGFRα/β), c-Kit, and other kinases. It exerts antiangiogenic and antitumor effects by inhibiting tumor blood vessel formation and tumor cell proliferation. - **Temozolomide** is an oral alkylating agent that methylates DNA at the O6 position of guanine, leading to DNA damage and apoptosis. It is widely used in the treatment of glioblastoma multiforme (GBM) and other brain tumors. The combination has been reported as a novel therapeutic approach for recurrent glioblastoma multiforme, representing the first application of almonertinib in this context. The rationale behind this regimen includes targeting multiple oncogenic pathways—EGFR signaling, angiogenesis, and direct cytotoxicity—to overcome resistance mechanisms often seen with monotherapy[10].