Four decades of glioblastoma targeted therapy: a bibliometric and pharmacological perspective on translational failure and future directions

Glioblastoma (GBM) remains highly resistant to targeted therapy despite four decades of molecular and translational research. To clarify the evolution and persistent translational barriers of this field, we performed a bibliometric and pharmacological analysis of 5,037 Web of Science Core Collection publications on GBM targeted therapy from 1985 to 2025. VOSviewer, CiteSpace, and bibliometric mapping approaches were employed to visualize research output by country/region, institution, author, journal, citation pattern, keyword co-occurrence, and thematic evolution. Over the past 40 years, research on GBM targeted therapy has grown rapidly, with 5,037 publications showing a sustained upward trend. The United States and China were the leading contributors, and the University of California, Los Angeles was among the most productive institutions. The field evolved through four major phases: molecular discovery, first-generation tyrosine kinase inhibitor development, anti-angiogenic therapy, and delivery-centered strategies. Key research hotspots include EGFR signaling, angiogenesis inhibition, blood–brain barrier penetration, nanoparticle delivery, receptor-mediated transport, focused ultrasound-mediated BBB disruption, immunotherapy, tumor microenvironment, and therapeutic resistance. Despite intensive research activity, clinical translation has remained limited, largely because many targeted agents fail to achieve adequate intratumoral exposure, durable target engagement, and effective distribution across infiltrative tumor regions. Current research on GBM targeted therapy focuses on three major challenges: overcoming blood–brain barrier restriction, addressing intratumoral heterogeneity and adaptive resistance, and integrating pharmacokinetic optimization with rational combination therapy. Addressing these obstacles is expected to advance GBM targeted therapy from biologically rational concepts toward clinically effective therapeutic strategies.