The Role of Blood–Brain Barrier in Brain Cancer: From Pathophysiology to Therapeutic Approaches

Brain tumors remain among the most lethal cancers, in part due to the limited ability of therapeutic agents to reach malignant cells protected by the blood-brain barrier (BBB). This specialized vascular interface preserves neural homeostasis through several mechanisms and different elements. In brain malignancies, the barrier may be disrupted, remodeled, or remain largely intact depending on tumor type, leading to highly variable effects on different therapeutic approaches. These challenges have driven the development of innovative delivery strategies, including molecular engineering, nanocarriers, receptor-mediated transport systems, focused ultrasound, and direct regional administration. Understanding BBB biology and its tumor-specific alterations is essential for designing effective therapeutic approaches capable of improving outcomes in brain cancer. Recent studies showed promising results with different approaches, including pharmacological approaches, nanotechnology-based approaches, physical disruption techniques, biological and cellular approaches, and convection-enhanced delivery. This review summarizes the current understanding of the role of BBB in brain cancer, and reviews emerging strategies to overcome this barrier and enable effective brain cancer therapy.