Regrettably, glioblastoma multiforme (GBM) remains the deadliest form of brain cancer, with a very unfavorable prognosis for life expectancy for the patient. We report, for the first time, the green colloidal synthesis of cobalt-doped magnetic iron oxide nanoparticles (Co-MNPs) as aqueous ferrofluids, using two anionic polysaccharide biopolymers, hyaluronic acid (HA) and carboxymethyl cellulose (CMC), as surfactants. These ferrofluids based on magnetite nanoparticles (HA@Co-MNP and CMC@Co-MNP) demonstrated superparamagnetic properties and magnetic-to-thermal conversion upon exposure to an alternating magnetic field (AMF), with the extent of conversion dependent on surfactant type. In addition, the ferrophase acted as a nanozyme, mimicking peroxidase-like activity in response to hydrogen peroxide, which is present at higher levels in tumor cells. The coupling of magnetic-heat capabilities with biocatalytic behavior enhances glioblastoma cell elimination and suppresses 3D neurospheroid growth. The results also showed that active targeting based on the HA biopolymer shell, due to its affinity for CD44 membrane receptors overexpressed in GBM, outperformed CMC-coated ferrofluid analogs. These magnetocatalytic-responsive nanoplatforms offer a broad avenue for the diagnosis and therapy of numerous cancers, potentially improving patients’ quality of life and prognoses.

Global, regional, and national epidemiology of childhood and adolescent brain and central nervous system cancers (1990-2021).

From neuropsychiatric use to oncology: Repurposing antipsychotic drugs for cancer treatment.

Stereotactic intracranial implantation of patient-derived glioblastoma cells in rats: A xenograft modeling approach.

A functionally relevant model for interrogating brain tumor-endothelial cell interactions.

Updated clinical practice guidelines for the management of adult diffuse gliomas.

Glioblastoma in New Zealand: A retrospective cohort analysis post WHO CNS 5.

Loss of function mutations of the Hedgehog receptor PTCH1 are oncogenic drivers in some skin and brain cancers. We recently reported mutations in exons encoding the C-terminal tail of PTCH1 in colon cancer, which result in premature truncation but do not impair canonical Hedgehog signalling. In this study, we show that colon cancer cells engineered by CRISPR/Cas9 to express endogenous truncated PTCH1 have enhanced proliferation, colony formation, anchorage-independent growth and form larger tumours in vivo than isogenic cells expressing wild-type PTCH1. Analysis of the mechanisms underlying this growth advantage revealed profound transcriptional changes and unexpectedly, upregulation of GLI1 and GLI2 by a Smoothened-independent route, which proved to be necessary for the proliferative advantage. Furthermore, we found that truncation of PTCH1 C-tail upregulated several cancer-related pathways, including EGFR and Ras signalling and led to enhanced GLI-dependent PI3K activation, which exerted a positive feedback regulation on GLI expression and activity. Accordingly, PTCH1 mutant cells were highly sensitive to PI3K and GLI inhibitors and were only partially sensitive to EGFR and MEK inhibitors. Altogether, these findings reveal that PTCH1 C-tail truncating mutations promote colon cancer tumourigenesis through a non-canonical GLI-PI3K positive loop.

Glioblastoma is an aggressive brain cancer with limited treatment options and poor patient survival, driven in part by cellular diversity within tumors. While individual cell types have been catalogued, how malignant, vascular, and immune cells are spatially organized inside human tumors remains incompletely understood. Here we show a spatially resolved, multi-modal atlas of human glioblastoma that integrates gene expression profiling across tissue sections with matched single-cell and protein measurements at subcellular resolution. Using a targeted 348 gene panel enriched for vascular and stromal markers, we identify less well-characterized endothelial, perivascular, and fibroblast-like cell states and define their spatial associations with malignant and immune compartments. We further identify a distinct oligodendrocyte population restricted to tumor core and perivascular regions that exhibits gene expression patterns associated with tumor recurrence and poor clinical outcome. This publicly accessible atlas provides a high-resolution framework for studying the spatial organization of glioblastoma and highlights region-specific cellular interactions that may represent therapeutically actionable vulnerabilities.

Brain tumour classification is a rapidly evolving field, with diagnostic evaluation integrating the latest in molecular testing techniques. As data in brain tumour registries and repositories are collected in real time, neuro-oncology researchers face clear challenges when analysing tumour cohorts diagnosed according to differing standards over time. This study aims to evaluate the impact of an evolving tumour classification system on both our institutional registry and widely used multi-institutional repositories in glioma translational research. Clinicopathological data, including molecular profiles, were obtained from the Sydney Brain Tumour Bank registry (1993-2025). We sourced available clinicopathological and molecular classification data from the Rembrandt and Gravendeel datasets, the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA). All cases were reclassified according to the WHO Classification of Tumours of the Central Nervous System (5th edition). Between 37% and 100% of cases diagnosed prior to the 2016 WHO Classification (revised fourth edition) require additional molecular testing for accurate diagnosis and grading. In contrast, the majority of cases in datasets established after the 2016 Classification met the WHO 2021 Classification criteria (61% to 97%). Two cohorts that consistently failed to meet 2021 requirements over time were high-grade gliomas in patients under 55 years and histological grade 2/3 IDH-mutant gliomas. An evolving tumour classification system necessitates regular review and reclassification of brain tumour datasets to ensure that brain cancer research is accurate and equitable. The reclassified datasets are provided for use by neuro-oncology researchers worldwide.

Abstract Background: Li-Fraumeni Syndrome (LFS), caused by pathogenic/likely pathogenic (P/LP) variants in TP53, is a cancer predisposition syndrome that increases the risk for numerous cancer types in both children and adults. Many studies have shown that cancer rates can vary between races and ethnicities. For example, the 2024 Cancer Statistics published by the American Cancer Society reported the incidence for breast cancer to be highest for White individuals and lowest for Hispanic/Latino individuals. One LFS study showed East Asian individuals were more frequently diagnosed with gastric cancer compared to North Americans and Europeans. Other studies identified P/LP TP53 variants associated with specific populations, such as the South and Southeast Brazil founder variant, p.Arg337His. However, there lacks extensive research on the variable expressivity of cancers within the LFS population, based on genotype, race, and/or ethnicity. This study aims to describe the specific TP53 germline variants, cancer rates, and cancer types among individuals of different racial and ethnic groups diagnosed with LFS. Methods: A retrospective chart review of individuals with germline P/LP TP53 variants at the University of Texas MD Anderson Cancer Center was completed. Data collected includes race, ethnicity, number of cancer diagnoses, cancer types, and location of the TP53 variant (exon and codon). Individuals with a suspected somatic TP53 variant were excluded from this study. Racial groupings included Asian, Black or African American, White, and Other/Unspecified. Ethnicity was categorized as Hispanic, Non-Hispanic, and Other/Unspecified. There were also six cancer type categories: adrenocortical carcinoma, brain cancer, breast cancer, osteosarcoma, soft tissue sarcoma, and non-core LFS cancers. Descriptive and statistical analyses, including chi-squared or Fisher’s exact tests and pairwise comparisons, were performed using R software (v4.4.1). Results: Two hundred and fifty individuals with a confirmed P/LP TP53 variant were included in the analysis. Breast cancer was the most common cancer type diagnosed for all ethnic and racial groups, except Asian individuals, who most frequently had non-core LFS cancer diagnoses. There was a significant difference in the rate of breast cancer across racial groups (p = 0.037), with Black or African American individuals with LFS having the highest rate of breast cancer at 76.5%. Additionally, individuals who identified as Black or African American were 1.87 times more likely to develop breast cancer in comparison to those who identified as White. For cancer rates, most individuals in each racial and ethnic group were diagnosed with one primary cancer. Statistical analysis did not identify a significant difference in cancer rates across groups defined by race or ethnicity. Regarding the location of variants within the TP53 gene, there was a significant difference in the rate of variants in exon four (p = 0.021) and exon six (p = 0.016) across racial groups, with variants in exon four being more common in Asian individuals (33.3%) and variants in exon six being more common in Black or African American individuals (35.3%). Conclusion: This study highlights similarities in the rates and types of cancers seen across racial and ethnic groups within a cohort of individuals with LFS. However, this study also identified potential differences in the rates of breast cancer and variant location across racial populations within the cohort. The results of this study provide information that can lead to more personalized counseling for patients and train risk models to accurately predict cancer risk for individuals with LFS of differing races and ethnicities. Citation Format: H. Esplen, B. Arun, C. DiNardo, H. Abdel-Salam, K. Richardson, C. Peterson, J. Corredor. Evaluating Cancer Rates, Cancer Types, and Variant Hotspots Across Races and Ethnicities in Individuals with Li-Fraumeni Syndrome [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-01-13.

The feasibility and accuracy of real-time intra-operative confocal tissue diagnosis in brain and spine cancer surgery.

Survivors of childhood brain tumors are at high risk of hypothalamic-pituitary dysfunction, but comparative data across cancer histotypes and treatment modalities are limited. This study evaluated the prevalence, risk factors, and timing of onset of hypothalamic-pituitary disorders in a large cohort of childhood brain cancer survivors, with attention to tumor type and therapeutic exposure. A retrospective cohort of 388 patients diagnosed with primary brain tumors before 18 years of age and followed at a tertiary center between 2000 and 2025 was analyzed. Demographic, clinical, and treatment data were extracted from medical records. Standardized endocrine assessments, including dynamic testing when indicated, were performed at diagnosis and throughout follow-up. Endocrine disorders were classified by international criteria, and onset timing was recorded. Glioma was the most frequent histotype (66.2%), followed by medulloblastoma (19.1%), ependymoma (6.2%), craniopharyngioma (5.2%), and germ-cell tumors (3.3%). Endocrine disorders occurred in 75.8% of patients, with the highest prevalence in craniopharyngioma and germ-cell tumors. Central hypothyroidism (27.8%) was the most common deficiency, followed by central precocious puberty (27.1%), growth hormone deficiency (25.8%), ACTH deficiency (22.7%), and central diabetes insipidus (16.8%). Early-onset deficiencies were typically related to surgical hypothalamic-pituitary injury, whereas late-onset disorders were mainly associated with radiotherapy or chemotherapy. Younger age at diagnosis and sellar/suprasellar localization independently predicted endocrine morbidity. This study provides a comprehensive analysis of endocrine outcomes by tumor histotype, treatment modality, and onset timeline, underscoring the need for individualized and lifelong endocrine surveillance in survivors of childhood brain tumors.

Glioblastoma (GBM) is a highly aggressive and lethal form of brain cancer with limited treatment options, particularly for recurrent cases. Oncolytic virus (OV) therapy is a novel therapeutic strategy for recurrent GBM, leveraging its ability to selectively target and destroy malignant cells while sparing surrounding healthy tissue. Recent clinical trials have indicated that oncolytic virotherapy has an acceptable safety profile and the potential to enhance survival in recurrent GBM. For instance, CAN-3110, a Nestin-promoter-driven herpes simplex virus-1 (HSV-1), demonstrated a median overall survival of 14.9 months in patients with recurrent GBM, with HSV-1 seropositive patients achieving more prolonged survival (14.2 versus 7.8 months in seronegative patients). This review aims to synthesize the current evidence on clinical outcomes in patients with recurrent GBM receiving oncolytic virotherapy, with a specific focus on safety profiles, therapeutic efficacy, and survival outcomes.

Glioblastoma, with a 5-year survival rate of just under 7.0%, is the most common form of brain cancer in adults. In this study, we evaluated the antiproliferative activity of the biopolymer p21-ELP1-Bac, a p21-derived peptide delivered via an elastin-like polypeptide (ELP1) carrier and a cell-penetrating peptide (CPP), across three glioblastoma cell lines: U87, GBM43, and GBM6. We assessed proliferation, cell cycle progression, and apoptosis to determine whether ELP-mediated intracellular delivery of p21-ELP1-Bac suppresses glioblastoma growth through cytostatic mechanisms rather than inducing apoptosis. Treatment with the modified protein effectively inhibited proliferation across all three lines, with U87 cells showing the greatest sensitivity and GBM6 cells demonstrating the greatest drug tolerance. Although apoptotic responses were generally low, they appeared more pronounced in GBM6 cells. Confocal microscopy revealed sustained cellular uptake and signal observed in both the cytoplasm and in proximity to the nucleus in all cell lines. Collectively, these findings indicate that p21-ELP1-Bac is efficiently internalized and capable of modulating proliferation across all three glioblastoma cell lines, supporting its further evaluation as a cytostatic delivery platform.

Immunotherapy targeting tumor-associated macrophages (TAMs) has emerged as a promising approach for treating glioma, driven by advances in drug discovery and development, including colony-stimulating factor 1 receptor (CSF1R) inhibitors. We previously developed a CSF1R inhibitor, C19, for TAM-targeting immunotherapy, which can reprogram TAMs and remodel the tumor immunosuppressive microenvironment. However, the application of CSF1R inhibitors in brain cancer is limited due to inefficient delivery across the blood-brain barrier (BBB). To address this limitation, we designed a brain-targeted liposomal delivery system (T12-Lipo) modified with the transferrin receptor-binding peptide T12. T12-Lipo can specifically bind to transferrin receptors, which are overexpressed in both the BBB and TAMs, thus enhancing the delivery efficiency of C19 across the BBB and to TAMs. This system promoted TAM repolarization toward an anti-tumor M1-like phenotype and thereby facilitated T-cell-mediated tumor killing. T12-Lipo improved the BBB permeability of C19, exhibiting significant therapeutic efficacy against glioma growth. The brain-targeted liposomal formulation of the CSF1R inhibitor C19 represents a promising and effective approach for glioma immunotherapy. T12 peptide-modified liposomes loaded with CSF1R inhibitor C19 can penetrate the BBB, promote M1 phenotypic differentiation of macrophages, effectively activate T-cell immunity, alleviate the tumor immunosuppressive microenvironment, and improve the therapeutic efficacy againstglioma.

Glioblastoma (GBM) remains the most aggressive primary adult brain cancer with limited therapeutic options. Our prior research demonstrated that androgen receptor antagonists (ARAs) enhance survival in GBM mouse models by preferentially suppressing glioma stem cells. This study investigates the potential of ARAs as radiosensitizers in combination with radiotherapy (RT). Combined effects of ARAs and RT were evaluated using an orthotopic GBM mouse model. RNA-Seq and TCGA analyses delineated AR-associated regulatory networks, while integrated cellular and molecular approaches utilizing human and mouse GBM cell lines, as well as in patient-derived primary high-grade glioma cultures, interrogated signaling and immune paradigms. ARA treatment induced G2/M cell cycle arrest, apoptosis, and downregulated DNA repair genes, with AR expression correlating with the DNA repair and TGF-β pathway. In both immortalized GBM cell lines and primary high-grade glioma cultured cells, ARAs in combination with RT showed only a modest enhancement of radiosensitivity. However, in an orthotopic GBM mouse model, ARA + RT demonstrated a strong synergy, achieving 100% long-term survival, compared to less than 50% with ARA alone and 0% with RT alone. Mechanistically, ARA modulated the TGF-β pathway, durably switching from Smad3 linker to c-terminal phosphorylation (pSmad3C) and inhibiting LIF/STAT3 axis. Distinct TGF-βs ligand expression patterns were observed in ARA-treated GBM cells. A protein–protein interaction noted between AR and Smad3, which was disrupted following ARA treatment, leading to elevated protein levels and nuclear localization of pSmad3C (S423/425), indicating normalization/activation of the TGF-β/pSmad3C-dependent anti-tumorigenic cascade. Comprehensive analyses in GBM cell lines and mouse model tissues demonstrated pathway reprogramming characterized by elevated TGF-β2 and increased pSmad3C. Tissue analysis revealed immune activation in the tumor microenvironment, while peripheral blood and spleen showed systemic immune responses following ARA + RT. Our study provides novel insights into how ARAs enhance RT efficacy through immunomodulation involving TGF-β/pSmad3C cascade, offering therapeutic implications in GBM.

The World Health Organization Global Initiative for Childhood Cancer has set a target of achieving a 60% survival rate by 2030. However, current evidence is insufficient to guide governments and medical institutions in developing the necessary policies and interventions to reach this goal. Therefore, it is imperative to systematically evaluate the current status and trends of childhood cancer survival worldwide. Focusing on mortality-to-incidence ratio (MIR), disability-adjusted life-years (DALY), and death, the study described the distribution and trends of these survival related indicators for childhood cancer using the data from GBD2021. The study characterized the disease spectrum of childhood cancer in Sociodemographic Index (SDI) regions and predicted the future trend using ARIMA mo MIR reflected the disparities in global countries and regions; Jointpoint model and age-period-cohort model were used to analyze the long-term trend; finally, the DALY of childhood cancer contribute to risk factors was assessed. In 2021, 25 level 3 childhood cancers contributed to 114.50 thousand (95% UI 104.70-124.31) death and 9343.21 thousand (95% UI 8529.00-10157.41) DALYs globally, and the MIR was 0.41 (IQR 0.26-0.58). In the high SDI region, brain and central nervous system cancers have ranked first in age-standardized DALY rate (AS-DALY) and age-standardized death rate (ASDR), and it is estimated that the AS-DALYs of nervous system cancer likely to surpass those of hematologic malignancy by 2024. The childhood cancer burden decreased with increasing SDI levels. The largest MIR [31.83 (95%UI 20.38-53.14)] between low and high SDI region was observed in eye cancer, followed by testicular cancer, Hodgkin lymphoma, and malignant skin melanoma (MIR > 10) in 2021. There has been a global downward trend in AS-DALYs and ASDR for childhood cancer; however, breast cancer has been increasing continuously. Although the number, rate, period risk, and cohort risks for childhood cancer DALY decreased across all SDI regions, the absolute burden increased by 35.92% (95% CI: 11.64 to 67.70) in low SDI region, with a concurrently observed rise in the absolute value and risks for nervous system cancer. Besides, the DALY rate of liver cancer attributable to drug use consistently increased, especially in high SDI region. This study identified several key points newly and could contribute to more precise recommendations for childhood cancer healthcare. It is imperative to pay more attention to the first rank on DALY of brain and central nervous system cancer in high SDI region, setting the priority to narrow the burden gap on retinoblastoma, testicular cancer, Hodgkin lymphoma, and malignant cutaneous melanoma through conducting more economical and inclusive interventions worldwide. Also, breast cancer and drug use-induced liver cancer should not be ignored.

Although direct biological factors underlying the progression of Glioblastoma (GBM), an aggressive form of brain cancer, have been extensively studied, emerging evidence suggests that indirect biological triggers, such as traumatic brain injury (TBI), may also have a role. Since proteoglycans, secreted by reactive astrocytes and astroglial cells contribute to biophysical characteristics (stochastic topography, stiffness) of the brain, we postulated a role for stochastic nanoroughness in the induction of glioma following brain trauma. Using a model system to emulate such physical cues that manifest following traumatic injury, we demonstrate that human cortical astrocytes undergo spontaneous organization into spheroids in response to nanoroughness and retain the spheroid phenotype even upon withdrawal of the physical cues. Furthermore, spheroids serve as aggregation foci for naïve astrocytes, express activated MMP2, and disseminate upon implantation in the mouse brain. RNA-seq analysis revealed that astrocytes within spheroids differentially express genes, including p53, ADAMTS proteases, and NOTCH3, and adopt a transcriptional program enriched for GBM proneural signatures, with reactome analysis pointing toward astrocytes with GBM-associated transcriptional traits. Moreover, nanoroughness mediates a cross-talk between cancer cells and astrocytes through induced senescence. These findings implicate a role for stochastic biophysical cues in driving a potential malignant transformation of astrocytes.

Comprehensive multi-omics analysis reveals RUNX1's prognostic value, immune associations, and MUC13-Mediated mechanistic role in hepatocellular carcinoma pathogenesis