The blood–brain barrier and strategies for drug delivery to brain tumors
Vihang Nakhate, Patrick Y. WenPurpose of review
Drug delivery across the blood–brain barrier (BBB) remains an important challenge in the treatment of brain tumors. This review summarizes the physiologic barriers to effective CNS drug exposure and evaluates strategies to improve delivery, with a focus on glioma.
Recent findings
Recent advances span three complementary approaches: engineering therapeutics for BBB penetration, transient BBB disruption, and locoregional delivery to bypass the BBB. Modern medicinal chemistry has enabled highly brain-penetrant agents such as vorasidenib, while transporter/receptor-mediated and nanocarrier platforms remain under investigation. Ultrasound with microbubbles has emerged as a leading strategy for spatially targeted, reversible BBB disruption, with early clinical studies demonstrating increased delivery of chemotherapies and monoclonal antibodies. Convection-enhanced delivery has benefited from improved catheter design, image guidance, and implantable systems, although efficacy in brain tumors remains unproven. Intratumoral oncolytic viruses and CSF-based cellular therapies are additional emerging approaches.
Summary
Strategies for drug delivery to brain tumors have advanced substantially, but translation remains challenging. Efficacious therapies must not only overcome the BBB but also achieve adequate exposure and target engagement across heterogeneous tumor regions. Future studies must pair active therapeutics with relevant delivery strategies, ascertain drug exposure and target engagement early through window-of-opportunity studies, and evaluate efficacy in randomized trials.