Search Results (318)

Background/Objectives: Medulloblastoma is the most common malignant brain tumor in children and comprises four molecular subtypes—WNT, SHH, Group 3, and Group 4—each with distinct genetic, epigenetic, and metabolic features. Increasing evidence highlights the critical role of metabolic reprogramming and epigenetic alterations in driving tumor progression, therapy resistance, and clinical outcomes. This review aims to explore the interplay between metabolic and epigenetic mechanisms in medulloblastoma, with a focus on their functional roles and therapeutic implications. Methods: A comprehensive literature review was conducted using PubMed and relevant databases, focusing on recent studies examining metabolic pathways and epigenetic regulation in medulloblastoma subtypes. Particular attention was given to experimental findings from in vitro and in vivo models, as well as emerging preclinical therapeutic strategies targeting these pathways. Results: Medulloblastoma exhibits metabolic adaptations such as increased glycolysis, lipid biosynthesis, and altered amino acid metabolism. These changes support rapid cell proliferation and interact with the tumor microenvironment. Concurrently, epigenetic mechanisms—including DNA methylation, histone modification, chromatin remodeling, and non-coding RNA regulation—contribute to tumor aggressiveness and treatment resistance. Notably, metabolic intermediates often serve as cofactors for epigenetic enzymes, creating feedback loops that reinforce oncogenic states. Preclinical studies suggest that targeting metabolic vulnerabilities or epigenetic regulators—and particularly their combination—can suppress tumor growth and overcome resistance mechanisms. Conclusions: The metabolic–epigenetic crosstalk in medulloblastoma represents a promising area for therapeutic innovation. Understanding subtype-specific dependencies and integrating biomarkers for patient stratification could facilitate the development of precision medicine approaches that improve outcomes and reduce long-term treatment-related toxicity in pediatric patients. Full article

This narrative review explores the integration of theranostics and artificial intelligence (AI) in neuro-oncology, addressing the urgent need for improved diagnostic and treatment strategies for brain tumors, including gliomas, meningiomas, and pediatric central nervous system neoplasms. A comprehensive literature search was conducted through PubMed, Scopus, and Embase for articles published between January 2020 and May 2025, focusing on recent clinical and preclinical advancements in personalized neuro-oncology. The review synthesizes evidence on novel theranostic agents—such as Lu-177-based radiopharmaceuticals, CXCR4-targeted PET tracers, and multifunctional nanoparticles—and highlights the role of AI in enhancing tumor detection, segmentation, and treatment planning through advanced imaging analysis, radiogenomics, and predictive modeling. Key findings include the emergence of nanotheranostics for targeted drug delivery and real-time monitoring, the application of AI-driven algorithms for improved image interpretation and therapy guidance, and the identification of current limitations such as data standardization, regulatory challenges, and limited multicenter validation. The review concludes that the convergence of AI and theranostic technologies holds significant promise for advancing precision medicine in neuro-oncology, but emphasizes the need for collaborative, multidisciplinary research to overcome existing barriers and enable widespread clinical adoption. Full article

Background. Medulloblastoma (MB) prognosis and response to therapy depend largely on genetic changes in tumor cells. Many genes and chromosomal abnormalities have been identified as prognostic factors, including amplification of MYC oncogenes, gains in 1q and 17q, deletions in 10q and 21p, or isochromosomes 17 (i(17)(q10)). The frequency of these abnormalities varies greatly between ethnic populations, but the frequency of specific abnormalities, such as MYCC and MYCN amplification, 17q gain, and deletions, in the Russian population is unknown. Objective: The aim is to study the frequency of MYCC and MYCN amplifications, 17q gain, and 17p deletion and determine their prognostic value in Russian patients with MB. Methods. This study was performed on MB cells obtained from 18 patients (12 boys and 6 girls, aged between 3 months and 17 years, with a median age of 6.5 years). Determination of cytogenetic aberrations was carried out using FISH assays with MYCC-SO, MYCN-SO, and MYCN-SG/cen2 probes, as well as cen7/p53 dual color probes and PML/RARα dual color probes (Abbott Molecular, USA). One-way ANOVA and Fisher’s F-test were used to compare the two groups. The differences were considered significant when p < 0.05. Results. In 77.7% of patients (14/18), the classical type of MB was present; in 16.7% (3/18), desmoplastic type; and in 5.6% (1/18), nodular desmoplasic types of neoplasms. Amplification of MYC genes was detected in 22.2% of Russian patients (n = 4 out of 18). Patients with MYC amplification had the worst overall survival (OS: 0% vs. 68%, p = 0.0004). Changes on the 17th chromosome were found in 58.3% of patients. Deletion of 17p occurred in 23.1%, and gain of 17q occurred in 46.2%. There were no significant differences in OS, clinical signs, or the presence of additional 17q material or 17p deletion among patients with MB. Conclusions: Amplification of the MYC gene is a predictor of poor overall survival to therapy and a high risk of metastatic relapse. This allows us to more accurately stratify patients into risk groups in order to determine the intensity and duration of therapy. Full article

Advances in molecular diagnostics have enabled precision medicine approaches in pediatric neuro-oncology, with small-molecule drugs emerging as promising therapeutic candidates targeting specific genetic and epigenetic alterations in central nervous system (CNS) tumors. This review provides a focused overview of several small-molecule agents under investigation or in early clinical use, including ONC201, tazemetostat, vorasidenib, CDK inhibitors, selinexor, and aurora kinase A inhibitors, among others. Highlighted are their mechanisms of action, pharmacokinetic properties, early efficacy data, and tolerability in pediatric populations. Despite encouraging preclinical and early-phase results, most agents face limitations due to study heterogeneity, lack of large-scale pediatric randomized trials, and challenges in drug delivery to the CNS. The review underscores the critical need for robust prospective clinical trials for the integration of these therapies into pediatric neuro-oncology care. Full article

Conventional chemotherapy continues to form the backbone of treatment for many pediatric central nervous system (CNS) tumors. Advances have been made especially in the molecular underpinning of certain pediatric CNS tumors, allowing for advancement and consideration in incorporating this molecular information in molecular targeted therapy or appropriate de-escalation or escalation of therapy. In very young children with embryonal CNS tumors, intensive high-dose chemotherapy approaches have been used with varied increased survival in medulloblastoma, atypical teratoid rhabdoid tumor (ATRT), and rare embryonal subtypes, but there are certain molecular risk groups that require new therapies, such as the ATRT MYC subtype. Some CNS tumors remain resistant or refractory to conventional chemotherapy, especially in relapsed disease. Strategies to explore combination therapies with chemotherapy, novel agents, and novel approaches are needed to improve survival in this population in the future. Full article

We report the first case of pleural mesothelioma (PM) occurring in a child affected by NF2-related schwannomatosis (NF2-SWN) and without any history of environmental exposure to asbestos. Mesothelioma is a rare secondary tumor in brain cancer patients and the association with NF2-SWN has been described only in a few anecdotal cases and never in the pediatric field. NF2-SWN is an autosomal dominant disease caused by inactivating germline mutations of the NF2 tumor suppressor gene, one of the most common mutations associated with human primary mesothelioma too. By MLPA assay, array-CGH analysis, and NGS on blood and tumor DNA, we determined the mutation profile of this rare NF2-driven PM and we identified several atypical chromosomal aberrations in tumor cells, suggesting a different genomic signature between pediatric and adult mesothelioma. Full article

The hypothalamic-pituitary-adrenal (HPA) axis plays an important regulatory role in inflammatory responses to systemic or local infection in the host. A high-calorie diet, which can aggravate pediatric pneumonia and delay recovery, is intimately associated with HPA axis disorder; however, its underlying mechanisms remain unknown. This study examined whether the mechanism by which a high-calorie diet aggravates pneumonia is related to HPA axis disorder. In this study, juvenile rats were fed a high-calorie diet and/or nebulized with lipopolysaccharide (LPS) for model construction. Our data shows that a high-calorie diet increases interleukin-1 beta(IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) levels in lung tissues and aggravates LPS-induced inflammatory injury in the lungs of juvenile rats. Additionally, we found that a high-calorie diet decreases the expression level of serum adrenocorticotropic hormone (ACTH) and corticosterone (CORT) in juvenile rats with pneumonia, resulting in HPA axis disorder. Hypothalamus proteomics and Western blot results proved that a high-calorie diet upregulated the expression level of hypothalamus hypoxia-inducible factor-1 alpha (HIF-1α) in juvenile rats with pneumonia, and this mechanism is associated with reduced HIF-1α ubiquitination. We further observed that HPA axis disorder was significantly abated and inflammatory damage in rat lung tissues was significantly alleviated after in vivo HIF-1α pathway inhibition. This shows that pneumonia aggravation by a high-calorie diet is associated with interference in the HIF-1α-mediated HPA axis. A high-calorie diet boosts HIF-1α signaling in the hypothalamus and exacerbates LPS-induced pneumonia by disrupting the HPA axis. This sheds light on lung inflammation and strengthens the lung-brain connection. Full article

Pediatric high-grade gliomas (pHGGs), particularly diffuse midline gliomas (DMGs), are among the most lethal brain tumors due to poor survival and resistance to therapies. DMGs possess a distinct genetic profile, primarily driven by hallmark mutations such as H3K27M, ACVR1, and PDGFRA mutations/amplifications and TP53 inactivation, all of which contribute to tumor biology and therapeutic resistance. Developing physiologically relevant preclinical models that replicate both tumor biology and the tumor microenvironment (TME) is critical for advancing effective treatments. This review highlights recent progress in in vitro, ex vivo, and in vivo models, including patient-derived brain organoids, genetically engineered mouse models (GEMMs), and region-specific midline organoids incorporating SHH, BMP, and FGF2/8/19 signaling to model pontine gliomas. Key genetic alterations can now be introduced using lipofectamine-mediated transfection, PiggyBac plasmid systems, and CRISPR-Cas9, allowing the precise study of tumor initiation, progression, and therapy resistance. These models enable the investigation of TME interactions, including immune responses, neuronal infiltration, and therapeutic vulnerabilities. Future advancements involve developing immune-competent organoids, integrating vascularized networks, and applying multi-omics platforms like single-cell RNA sequencing and spatial transcriptomics to dissect tumor heterogeneity and lineage-specific vulnerabilities. These innovative approaches aim to enhance drug screening, identify new therapeutic targets, and accelerate personalized treatments for pediatric gliomas. Full article

Proton therapy is increasingly used to treat pediatric and adult brain tumors, but there is still uncertainty surrounding the biological effects of protons on the heart. Also, the molecular and functional responses to proton irradiation are still unknown. This study investigates the effect of protons on cardiac disease by comparing their effects on the hearts of rats exposed to hypergravity. A total of 20 Sprague Dawley rats were tested, including a group that was irradiated with 0.1 Gy of protons to the heart, a group exposed to hypergravity, a group exposed to both protons and hypergravity, and a control group. Changes in AQP4, calcium homeostasis, and fibrosis-related markers were investigated using Western blotting, immunohistochemistry, etc. The proton-irradiated group showed no changes compared to the control group. In rats exposed to hypergravity, the cardiac fibrosis markers TGF-ꞵ1, MMP9, and MMP2 were increased. On the other hand, the group exposed to hypergravity followed by proton irradiation tended to display a significant decrease in these markers. Along with reduced fibrosis-related markers, the consistent tendency was also confirmed in the cardiac calcium homeostasis-related proteins and AQP4 through Western blotting. In summary, our findings indicate that rats subjected to hypergravity experienced both cardiac hypertrophy and fibrosis, while proton therapy appeared to mitigate the effects of cardiac disease. These results suggest that proton therapy prevents heart disease triggered by hypergravity, providing insights for protecting astronauts’ cardiovascular health. Full article

Background: High-grade glioma (HGG) is the most common primary malignant brain tumor, with peak incidence in the fifth and sixth decades of life. Although HGG is rare in children, the prognosis remains poor, with a median overall survival (OS) of less than two years. Recently, TRK inhibitors have been approved for the treatment of tumors harboring NTRK gene fusions. In this review, we analyzed data from early clinical trials investigating the use of these agents in patients with HGG. Methods: A systematic literature search was performed in the PubMed database. Studies involving patients with HGG treated with TRK inhibitors were included. We analyzed progression-free survival (PFS), 24-week disease control rate, and complete or partial radiological responses according to the Response Assessment in Neuro-Oncology (RANO) criteria. Results: Sixteen studies comprising 55 patients with HGG harboring NTRK gene fusions (19 adults and 36 children) were included. A statistically significant difference in PFS was observed between pediatric and adult patients treated with TRK inhibitors (17 vs. 8.5 months; p < 0.001). Pediatric patients also exhibited a higher rate of complete or partial radiological response compared to adults (94% vs. 57%). Discussion: Although the available evidence on TRK inhibitors in HGG is limited, the findings of this review highlight a potentially promising role for these agents, particularly in the treatment of pediatric HGGs. Full article

Background: Pediatric high-grade glioma (pHGG) is a highly aggressive cancer with unique biology distinct from adult high-grade glioma, limiting the effectiveness of standard treatment protocols derived from adult research. Objective: The purpose of this report is to present preliminary results from an ongoing pilot study integrating spectroscopic magnetic resonance imaging (sMRI) to guide proton beam therapy and longitudinal imaging analysis in pediatric patients with high-grade glioma (pHGG). Methods: Thirteen pediatric patients under 21 years old with supratentorial WHO grade III-IV glioma underwent baseline and serial whole-brain spectroscopic MRI alongside standard structural MRIs. Radiation targets were defined using T1-weighted contrast enhanced, T2-FLAIR, and Cho/NAA ≥ 2X maps. Longitudinal analyses included voxel-level metabolic change maps and spatial overlap metrics comparing pre-proton therapy and post-. Results: Six patients had sufficient longitudinal data; five received sMRI-guided PBT. Significant positive correlation (R² = 0.89, p < 0.0001) was observed between T2-FLAIR and Cho/NAA ≥ 2X volumes. Voxel-level difference maps of Cho/NAA and Choline revealed dynamic metabolic changes across follow-up scans. Analyzing Cho/NAA and Cho changes over time allowed differentiation between true progression and pseudoprogression, which conventional MRI alone struggles to achieve. Conclusions: Longitudinal sMRI enhanced metabolic tracking in pHGG, detects early tumor changes, and refines RT targeting beyond structural imaging. This first in-kind study highlights the potential of sMRI biomarkers in tracking treatment effects and emphasizes the complementary roles of metabolic and radiographic metrics in evaluating therapy response in pHGG. Full article

Pediatric central nervous system (CNS) tumors, including gliomas, medulloblastomas, and diffuse midline gliomas (previously diffuse intrinsic pontine gliomas), remain a major clinical challenge due to their complex biology, limited treatment effectiveness, and generally poor prognosis. Standard treatments are often aggressive and associated with substantial toxicity, particularly in advanced stages. This review highlights recent developments in radiopharmaceuticals for molecular imaging and targeted radiotherapy. A comprehensive literature analysis was conducted, focusing on radiotracers with clinical relevance in pediatric neuro-oncology, including metabolic, peptide receptor-based, and antibody-based agents. Radiopharmaceuticals such as ¹⁸F-FLT, ⁶⁴CuCl₂, and 1-L-18F-FETrp have improved the ability to monitor tumor biology, proliferation, and treatment response, aiding in diagnosis at an early stage, assessment of tumor behavior, and detection of recurrence or progression. Additionally, peptide receptor-based radiotracers, such as ⁶⁸Ga-DOTATATE and ¹⁷⁷Lu-DOTATATE, are already used for both diagnostic purposes and targeted radiotherapy, particularly in neuroblastomas and gliomas. Antibody-based radiotracers like ¹³¹I-omburtamab, targeting B7-H3, are emerging as promising tools for addressing difficult-to-treat tumors such as diffuse midline glioma. Collectively, these advances provide new hope for children afflicted by these devastating malignancies, offering promising solutions for more specific and precise diagnosis and, additionally, for more effective, personalized, and less toxic tumor therapies. Full article

Background/Objectives: Medulloblastoma is a rare tumor that represents almost two-thirds of all embryonal pediatric brain tumor cases. Current treatments, including surgery, radiation, and chemotherapy, are often associated with adverse effects, such as toxicity, resistance, and lack of specificity. According to multiple bulk and single-cell omics-based approaches, it is now clear that each molecular subgroup of medulloblastoma possesses intrinsic genetic and molecular features that could drive the definition of distinct therapeutic targets, and of markers that have the potential to improve diagnosis. Nanomedicine offers a promising approach to overcome these challenges through precision-targeted therapies and theranostic platforms that merge diagnosis and treatment. This review explores the role of nanomedicine in medulloblastoma. Here, possible theranostic nanoplatforms combining targeted drug delivery and simultaneous imaging are reviewed, highlighting their potential as tools for personalized medicine. Methods: We performed a chronological analysis of the literature by using the major web-based research platforms, focusing on molecular targets, and the potential application of nanomedicine to overcome conventional treatment limitations. Results: Advances in nanoparticle-based drug delivery systems enable selective targeting of key molecular pathways, improving therapeutic efficacy while minimizing off-target effects. Additionally, nanotechnology-based imaging agents, including MRI contrast agents and fluorescent probes, improve diagnostic accuracy and treatment monitoring. Despite these advantages, some significant challenges remain, including overcoming the blood–brain barrier, ensuring biocompatibility, and addressing regulatory pathways for clinical translation. Conclusions: In conclusion, we sought to identify the current knowledge on the topic and hope to inspire future research to obtain new nanoplatforms for personalized medicine. Full article

Glioblastoma is one of the most aggressive and lethal forms of brain cancer, with limited therapeutic options and poor patient prognosis. Recent research has identified the TMED family of proteins as key regulators of tumor progression and aggressiveness across multiple cancer types. TMED members are cargo receptors expressed within the early secretory pathway and involved in bidirectional traffic of various proteins including EGFR, TGF-ɑ and WNT. In this study, we explored the therapeutic potential of genetic and pharmacologic inhibition of the cargo receptor TMED9 in glial tumor models. Our findings demonstrate that TMED9 expression is upregulated in glioma and that this upregulation is associated with poor patient survival. Using patient-derived glioma tumor cells, we demonstrate that TMED9 is highly expressed in the cancer stem cell population and that this upregulation promotes the cells’ self-renewal and migration. This is the first time, to the best of our knowledge, that TMED9 has been shown to play a major role in the function and tumorigenesis of brain tumor cancer stem cells. BRD4780, a small molecule that targets TMED9, effectively reduced TMED9 abundance, resulting in decreased viability, migration and stemness of patient-derived glioma stem cells. Moreover, BRD4780 mitigated the proliferation and migration of differentiated glioma tumor cells. When applied together with temozolomide, an established glioblastoma treatment, BRD4780 elicited an enhanced anti-tumor response. Lastly, to demonstrate the broad applicability of our findings, we targeted TMED9 in pediatric glioma cells and showed efficient inhibition of various oncogenic functions. Collectively, our study identifies TMED9 inhibition as a promising therapeutic approach that impairs the tumorigenesis and aggressiveness of brain tumors, with high efficacy against the tumor stem cell population. The effectiveness of TMED9 targeting in different tumor cell populations, the potential of combining this strategy with established therapies and the broad applicability of this approach to multiple cancer types highlight the significance of these findings. Full article

Pediatric central nervous system (CNS) tumor survivors are highly susceptible to long-term toxicity due to tumor location and also the treatment received. Advancements in treatment techniques, risk-adapted approaches to therapy with adjustments to treatment regimens—including de-escalation when feasible—along with the addition of supportive therapy and surveillance in these survivors, serve to minimize and manage late effects of therapy. Full article