temozolomide + valproic acid + vinorelbine

This is a combination regimen consisting of three drugs—temozolomide, valproic acid, and vinorelbine—used primarily in the treatment of high-grade gliomas such as anaplastic astrocytoma and glioblastoma, particularly in pediatric and young adult populations. Temozolomide is an oral alkylating agent that induces DNA damage by methylating guanine residues, leading to cell death. Valproic acid is a histone deacetylase inhibitor with antiepileptic properties that can enhance the anticancer effects of temozolomide through epigenetic modulation, induction of apoptosis (notably via p53–PUMA pathway), disruption of DNA repair pathways, and autophagy induction. Vinorelbine is a semi-synthetic vinca alkaloid that inhibits mitosis by binding tubulin and disrupting microtubule formation during cell division. The combination aims to improve survival outcomes by leveraging complementary mechanisms—DNA damage (temozolomide), epigenetic sensitization (valproic acid), and mitotic inhibition (vinorelbine). Clinical studies have shown this regimen to be feasible with manageable toxicity in children with high-grade gliomas[1][4][6].