All literature data were obtained from the Web of Science Core Collection, a comprehensive database of globally influential research publications. The search was conducted on March 1, 2025, using the following query:TS = ((glioma OR gliomas OR “malignant glioma” OR “glioblastoma”) AND (“pharmacotherapy” OR “drug therapy” OR “chemotherapy”)), covering the period from January 1, 2020, to December 31, 2024. This search yielded 21,477 records. To ensure relevance and data reliability, non-academic documents-including letters, editorials, calls for papers, book reviews, and conference announcements-were excluded, resulting in a final dataset of 9,701 valid articles. The search tactics are depicted in Figure 1.

We extracted bibliographic data from the Web of Science Core Collection, including titles, authors, publication years, countries/regions, institutions, keywords, citations, abstracts, and references. The data were downloaded in plain text format. VOSviewer was used to generate collaboration networks for authors, institutions, and countries/regions, as well as keyword co-occurrence and clustering maps. Citespace was applied to analyze keyword bursts and construct timeline visualizations. VOSviewer can be downloaded from https://www.vosviewer.com/, and Citespace is available at https://citespace.podia.com.

To ensure the thematic coherence and interpretability of the clustering results, we performed manual validation following automated keyword clustering. Representative keywords within each cluster were reviewed to assess their semantic consistency, and a sample of highly cited articles associated with each cluster was examined to confirm alignment with the identified themes. This process helped verify the robustness and relevance of the clustering output.

The annual number of publications reflects the academic development of a field (8). From 2020 to 2024, 9,701 glioma-related articles were published, as shown in Figure 2. The publication volume increased steadily from 2020 to 2022, with a significant rise in 2021 and peaking at 2,134 articles in 2022. Publication volume declined in 2023 and 2024, which may be attributed to a combination of factors, including the lingering effects of the COVID-19 pandemic, publication and indexing delays, shifting research priorities, and potential saturation of certain research topics. Nonetheless, the overall trend remained relatively stable.

Figure 3a visualizes the collaboration networks among authors in glioma research. Each node represents an author, and the connections between nodes indicate collaborative relationships. The network includes 15 authors with over 20 publications, five with over 30, and one with more than 40 publications, reflecting a high level of productivity and positive growth in the field. The top five authors are all from China, with Liu Yang (41 publications) being the most prolific, highlighting China's rapid progress in this area. The density and distribution of the connections suggest several cohesive domestic research teams with strong interactions, while international research appears more fragmented, though there is some collaboration between domestic and international teams.

Glioma research has a long-standing history, with scholars from various countries contributing extensively to the establishment of a robust academic foundation. In recent years, a growing number of emerging researchers from China have produced a high volume of publications, positioning the country as a leading force in the field and underscoring its rapid progress in glioma research (Figure 3b).

Using VOSviewer, we visualized the key institutions and their collaboration networks, as shown in Figure 3c. The analysis reveals that higher education institutions and research organizations dominate the field, reflecting their central role in glioma research. Chinese institutions, particularly Shandong University, Nanjing Medical University, and Capital Medical University, play a leading role. These institutions exhibit strong, balanced collaboration, creating a dynamic and thriving research environment.

Figure 3d illustrates that glioma research abroad began earlier, with institutions like Harvard Medical School and Johns Hopkins University leading the way. In China, early contributors include Shandong University, China Medical University, and National Taiwan University. In recent years, numerous domestic institutions have achieved considerable advancements, contributing to the development of a comprehensive and multi-layered research network in the field.

Figure 4a shows the distribution of publications in glioma research across countries. China ranks first globally in publication output, with the United States following closely behind. Research is primarily concentrated in developed countries in Europe and North America. Using VOSviewer, we analyzed the collaborative relationships among major countries and regions (Figure 4b). Figure 4c reveals that developed countries, led by the United States, began their research in this field earlier. China has experienced rapid growth in recent years. In contrast, some developing countries in Asia and Africa have only recently started to emerge in this area.

Keywords are concise summaries of the main themes in literature. Analyzing keywords can reveal research trends, hotspots, and connections between themes in a field. In this study, we used Citespace and VOSviewer to analyze keywords (Figure 5a). The results show that terms such as “glioblastoma,” “glioma,” “expression,” “apoptosis,” “tumor,” and “temozolomide” are highly frequent keywords. These keywords form a complex network with extensive radiating connections to other terms like “nanoparticles,” “blood-brain barrier,” “immunotherapy,” “central nervous system,” “proliferation,” and “treatment.” This indicates that the field of glioma research has developed a well-defined content system.

Based on the keyword co-occurrence network, we clustered keywords with similar characteristics to create a clustering map in the field of glioma research (Figure 5b). The keywords were divided into 15 clusters: #0 glioma, #1 drug resistance, #2 cancer stem cells, #3 combination therapy, #4 tumor treatment, #5 glioblastoma, #6 lncRNA, #7 targeted therapy, #8 brain tumors, #9 extracellular vesicles, #10 temozolomide, #11 blood-brain barrier, #12 cell cycle, #13 biomimetic nanoparticles, #14 tumor microenvironment, and #15 drug repurposing. By merging similar cluster terms and integrating high-frequency keywords, we identified two main research directions in glioma studies: immunotherapy and tumor microenvironment, and drug delivery for glioma treatment.

Keyword burst and time-zone analyses (Figures 5c, d) reveal the historical evolution of glioma research by identifying emerging trends and the longevity of research hotspots. In 2020, 18 new keywords emerged, including “blood-brain barrier,” “neural stem cells,” and “endothelial cells.” In 2021, additional keywords such as “Wnt signaling protein,” “case report,” “immune checkpoint inhibition,” and “radiosensitivity” appeared. By 2022, terms such as “immune infiltration,” “preclinical models,” and “neurodegenerative diseases” began to gain prominence and have maintained their relevance through 2024, reflecting sustained and growing research interest in these areas. The year 2020 marked a peak in keyword emergence, with 18 new terms introduced. Among these, “immune infiltration” had the highest burst strength (7.31), underscoring its prominence as a major research hotspot in the field.

Bibliometric analysis offers a comprehensive overview of research trends in glioma pharmacotherapy. China and the United States are the leading contributors in this field, with both countries generating a substantial volume of high-quality research. This prominence reflects their robust research infrastructures and considerable investments in the field of neuro-oncology. Notably, collaborations between Chinese and U.S. scientists have contributed to important progress in glioma research, including studies on brain metastases at the single-cell level (9) and neural circuit interactions in glioblastoma (10). These efforts have enhanced our understanding of tumor biology and highlight how international cooperation can drive innovation and high-impact discoveries in the field. Additionally, countries in Europe, Asia, and the Americas contribute to the globalization of glioma research, each focusing on specific areas. For example, Europe has become a leader in innovative immunotherapy research (11, 12). Although China and the United States dominate in publication output, there is a modest but noticeable increase in contributions from developing regions. Continued growth may be supported by enhanced international collaboration, targeted funding, and improved access to research infrastructure and publishing platforms.

Keyword analysis reveals major focus areas in glioma pharmacotherapy. High-frequency terms like “glioblastoma,” “temozolomide,” and “immunotherapy” form a strong research network, indicating their central role in current studies. The frequent appearance of terms like “immune infiltration” and “immunotherapy” shows the rising prominence of immune-based approaches, reflecting substantial advances in tumor immunology (13, 14). Additionally, the continued emphasis on keywords such as “blood-brain barrier” and “drug delivery” underscores the ongoing challenge of overcoming the blood-brain barrier to enhance drug efficacy (15, 16).

Regarding research trends, 2020 marked a surge in keyword emergence, signaling the rapid expansion of glioma research. Recent keywords like “neurodegenerative disease” and “preclinical modeling” suggest that research is increasingly shifting toward understanding basic mechanisms and advancing translational medicine (17, 18). This trend aligns with neuro-oncology's aim to develop better therapies through deeper insights into tumor biology.

Chemotherapy, particularly TMZ, has been the standard treatment for glioblastoma for many years. TMZ induces DNA damage, causing cell cycle arrest and apoptosis in tumor cells (19). However, resistance to TMZ is common, driven by mechanisms such as MGMT promoter methylation and other genetic alterations (20). To overcome these challenges, combination therapies integrating TMZ with agents like radiation therapy or immunotherapy are being explored (21, 22). Immunotherapy has emerged as a promising approach in glioma treatment. Immune checkpoint inhibitors, such as anti-PD-1 and anti-CTLA-4 antibodies, enhance the immune system's ability to target tumor cells (23, 24). However, the response to these therapies is often limited by the immunosuppressive tumor microenvironment (TME). Recent studies indicate that combining immune checkpoint inhibitors with treatments like radiation therapy or CAR-T cell therapy can improve therapeutic outcomes (25, 26).

Combining pharmacotherapy with immunotherapy has shown promise in both preclinical and clinical studies. For instance, a phase 2 trial combining TMZ with pembrolizumab (an anti-PD-1 antibody) and TTFields demonstrated improved progression-free survival in newly diagnosed glioblastoma patients (27). Additionally, oncolytic viruses, which selectively infect and destroy tumor cells while stimulating an immune response, have shown synergistic effects when combined with immune checkpoint inhibitors (28–30). Future research should focus on optimizing combination therapies to maximize efficacy and minimize toxicity. Exploring new targets within the TME, such as the cGAS-STING pathway, could provide potential for reprogramming the immune response. Moreover, addressing the challenges of the BBB is crucial, as effective drug delivery to the brain is essential for successful treatment. The emergence of keywords such as “immune infiltration” underscores the increasing attention to the tumor microenvironment in glioma, particularly the role of immune cells in modulating tumor progression and response to immunotherapies.

The keyword “immune infiltration” showed the strongest burst strength in our bibliometric analysis, highlighting the growing recognition of immune cells-including tumor-associated macrophages, T cells, and microglia-as key regulators of glioma progression and treatment responsiveness. This trend reflects a paradigm shift toward therapeutic strategies that not only target tumor cells directly but also modulate immune dynamics within the TME to enhance the success of immunotherapy. Although immunotherapy has attracted increasing research interest, its clinical application in glioma remains limited, with most approaches still being evaluated in early-phase trials or exploratory combination regimens (31, 32).

The BBB is a major obstacle in glioma treatment, as its selective permeability limits the entry of therapeutic agents into the brain. Extensive research has focused on strategies to enhance drug delivery across the BBB and increase its permeability. These strategies can be categorized into physical, chemical, and biological methods. Physical approaches, such as focused ultrasound (33), andmicrobubble-assisted delivery (34), transiently disrupt the BBB, increasing its permeability without causing permanent damage. Chemical methods, including receptor-mediated transcytosis (RMT), utilize the natural transport mechanisms of the BBB to facilitate drug delivery. Biological approaches involve functionalizing nanocarriers with ligands targeting specific receptors on endothelial cells, such as transferrin receptor (35), to improve drug delivery efficiency through RMT.

Nanotechnology has emerged as a promising solution for overcoming the BBB in glioma treatment. Among the emerging nanoparticle platforms, exosomes, polymeric micelles, and biomimetic nanocarriers have gained increasing prominence in recent glioma research (36, 37). Exosomes, as naturally occurring extracellular vesicles, offer intrinsic advantages such as high biocompatibility, low immunogenicity, and innate ability to cross the BBB. Polymeric micelles, with their core-shell architecture, are particularly useful for encapsulating hydrophobic drugs and enabling sustained release. In addition, biomimetic nanoparticles—engineered by coating synthetic carriers with cell membranes [e.g., leukocytes (38), platelets (39), or glioma cells (16)]—enhance immune evasion, prolong circulation time, and improve targeting specificity. These advanced delivery systems represent a promising frontier in overcoming the physiological barriers to effective glioma treatment and are increasingly highlighted.

The frequent appearance of keywords such as “nanoparticles” in recent literature reflects the growing interest in nanotechnology-based delivery systems, which offer a viable strategy to bypass the BBB and deliver chemotherapeutic or immunomodulatory agents more effectively to glioma tissues. This aligns with ongoing efforts to improve drug bioavailability and therapeutic outcomes through innovative formulation techniques. Notably, several early-phase clinical trials—such as NCT03566199, NCT04881032, and NCT03020017—have been initiated to evaluate the clinical potential of nanoparticle-based approaches for glioma therapy. However, most remain in Phase I/II, indicating that while preclinical data are promising, clinical translation is still in its early stages. These observations suggest that high-frequency keywords like “nanoparticles” reflect emerging innovation rather than widespread clinical adoption, underscoring both the promise and the ongoing challenges of translating nanotechnology into approved therapies.