Role of matrix metalloproteinases in the invasion of glioblastoma and drug interventions (Review)

Glioblastoma (GBM) is the most aggressive primary malignant brain tumor type in adults, and is characterized by high invasiveness, therapeutic resistance and recurrence. Current treatments, primarily surgery combined with radiotherapy and chemotherapy, offer limited efficacy, thus necessitating more effective interventions. Matrix metalloproteinases (MMPs) crucially contribute to GBM progression through extracellular matrix degradation, epithelial‑mesenchymal transition and angiogenesis. MMP expression is intricately regulated by signaling pathways, non‑coding RNAs and the tumor microenvironment. Recently, strategies targeting MMPs have gained attention, including natural active substances and small‑molecule compounds with promising therapeutic potential. Nano‑delivery systems have notably improved drug delivery efficiency to the brain by overcoming the blood‑brain barrier, and combination therapies have demonstrated enhanced efficacy. However, chemotherapy resistance and functional heterogeneity remain critical challenges. The present review summarizes recent advances in understanding MMP regulatory mechanisms in GBM, highlighting the roles of signaling pathways and non‑coding RNAs. Additionally, the therapeutic potential of natural products, small‑molecule inhibitors, smart nanocarriers and combination treatments are discussed. Future research should focus on identifying novel inhibitors, and leveraging interdisciplinary approaches to facilitate precision‑targeted drug development, thereby addressing current treatment bottlenecks in GBM.