Pediatric Central Nervous System Tumor Overview and Emerging Treatment Considerations

Damodharan, Sudarshawn; Puccetti, Diane

doi:10.3390/brainsci13071106

Cited by 5 publications

(3 citation statements)

References 91 publications

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“…It has been used to identify important genes that may serve as biomarkers and specific molecular targets for treatment [37,88]. Further, CNS tumors have become the primary tumor emerging in pediatric patients [17,27,60,89]. CNS tumors are often associated with debilitating diseases or conditions, such as seizure, stroke, brain edema, severe headaches, mental disorders, neurocognitive impairment, and ultimately cancer [7,90,91].…”

Section: Discussionmentioning

confidence: 99%

Analysis of Gene Expression Networks in Primary Central Nervous System Tumors for Drug Repurposing Prospects

Villanueva,

Tsai,

Tayo

2023

Preprint

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Primary central nervous system and brain tumors are one of the global burdens that are continuously increasing in cases and requiring more treatment options. Surgery has been the leading treatment option for tumors, however, the localization of the tumor and its infiltrating nature make this option challenging. DNA microarray expression profiles of different CNS tumors provide insight into potential biomarkers for identifying different tumor types and subtypes. Here, we utilized the differentially expressed genes common in four expression profiles, GSE66354, GSE68848, GSE74195, and GSE43290 to reconstruct the gene co-expression network. In this study, we were able to identify preserved cluster genes, hub genes, co-regulating transcription factors, miRNA families, and candidate repurposed drugs. Fourteen identified hub genes, which were, CACNA1A, DNM1, GABRA1, GRIA2, MAPT, SLC17A7, SNAP25, SNAP91, STXBP1, SYT1, COL1A1, COL6A2, FBN2, and FN1 appeared to play a role in tumor progression and may serve as drug targets. We also reported the DEGs in each tumor type, which were ATRT, EPN, PA, MED, PNET, MEN, ACM, ODG, and GBM. Five identified miRNA families, which were, let-7 family, mir-124 family, mir-1 family, mir-103 family, and mir-27 family described in the literature to have tumor-suppressing characteristics. Drug-gene and drug-transcription factor network revealed 32 candidate repurposed drugs and 13 were validated through connectivity map analysis. Here, two main repurposed drugs fit the regulatory requirement for gene interaction, these were, quercetin and vorinostat. Future validation in experimental studies may utilize the future use of the candidate repurposed drugs. Our study provides insights into drug repurposing prospects and understanding tumor expressions.

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Section: Discussionmentioning

confidence: 99%

Analysis of Gene Expression Networks in Primary Central Nervous System Tumors for Drug Repurposing Prospects

Villanueva,

Tsai,

Tayo

2023

Preprint

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“…Childhood Central Nervous System (CNS) tumors represent 25% of pediatric tumors and are the leading causes of cancer-related mortality in children [ 1 ]. The most common are low-grade gliomas, categorized by the WHO into four grades: I (pilocytic astrocytoma, PA), II (diffuse astrocytoma), III (anaplastic astrocytoma), and IV (glioblastoma multiforme) [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Proteomic Profiling of Cerebrospinal Fluid and Its Extracellular Vesicles from Extraventricular Drainage in Pediatric Pilocytic Astrocytoma, towards Precision Oncology

Spinelli,

Kajana,

Garbarino

et al. 2024

Cancers

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Pediatric pilocytic astrocytoma (PA) is the most common brain tumor in children. Complete resection provides a favorable prognosis, except for unresectable PA forms. There is an incomplete understanding of the molecular and cellular pathogenesis of PA. Potential biomarkers for PA patients, especially the non-BRAF-mutated ones are needed. Cerebrospinal fluid (CSF) is a valuable source of brain tumor biomarkers. Extracellular vesicles (EVs), circulating in CSF, express valuable disease targets. These can be isolated from CSF from waste extraventricular drainage (EVD). We analyzed the proteome of EVD CSF from PA, congenital hydrocephalus (CH, non-tumor control), or medulloblastoma (MB, unrelated tumoral control) patients. A total of 3072 proteins were identified, 47.1%, 65.6%, and 86.2% of which were expressed in the unprocessed total and in its large-EV (LEV), and small-EV (SEV) fractions. Bioinformatics identified 50 statistically significant proteins in the comparison between PA and HC, and PA and MB patients, in the same fractions. Kinase enrichment analysis predicted five enriched kinases involved in signaling. Among these, only Cyclin-dependent kinase 2 (CDK2) kinase was overexpressed in PA samples. PLS-DA highlighted the inactive carboxypeptidase-like protein X2 (CPXM2) and aquaporin-4 (AQP4) as statistically significant in all the comparisons, with CPXM2 being overexpressed (validated by ELISA and Western blot) and AQP4 downregulated in PA. These proteins were considered the most promising potential biomarkers for discriminating among pilocytic astrocytoma and unrelated tumoral (MB) or non-tumoral conditions in all the fractions examined, and are proposed to be prospectively validated in the plasma for translational medicine applications.

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“…High-grade gliomas (HGG) account for approximately 10% of central nervous system (CNS) tumors in children and 25% of CNS tumors in adults [1,2]. Despite their rare occurrence, they constitute a significant problem because of the perceived low efficacy of the currently used therapeutic methods.…”

Section: Introductionmentioning

confidence: 99%

Chimeric Antigen Receptor T Cell and Chimeric Antigen Receptor NK Cell Therapy in Pediatric and Adult High-Grade Glioma—Recent Advances

Kowalczyk,

Zarychta,

Marszołek

et al. 2024

Cancers

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High-grade gliomas (HGG) account for approximately 10% of central nervous system (CNS) tumors in children and 25% of CNS tumors in adults. Despite their rare occurrence, HGG are a significant clinical problem. The standard therapeutic procedure in both pediatric and adult patients with HGG is the surgical resection of the tumor combined with chemotherapy and radiotherapy. Despite intensive treatment, the 5-year overall survival in pediatric patients is below 20–30%. This rate is even lower for the most common HGG in adults (glioblastoma), at less than 5%. It is, therefore, essential to search for new therapeutic methods that can extend the survival rate. One of the therapeutic options is the use of immune cells (T lymphocytes/natural killer (NK) cells) expressing a chimeric antigen receptor (CAR). The objective of the following review is to present the latest results of preclinical and clinical studies evaluating the efficacy of CAR-T and CAR-NK cells in HGG therapy.

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Pediatric Central Nervous System Tumor Overview and Emerging Treatment Considerations

Cited by 5 publications

References 91 publications

Analysis of Gene Expression Networks in Primary Central Nervous System Tumors for Drug Repurposing Prospects

Analysis of Gene Expression Networks in Primary Central Nervous System Tumors for Drug Repurposing Prospects

Proteomic Profiling of Cerebrospinal Fluid and Its Extracellular Vesicles from Extraventricular Drainage in Pediatric Pilocytic Astrocytoma, towards Precision Oncology

Chimeric Antigen Receptor T Cell and Chimeric Antigen Receptor NK Cell Therapy in Pediatric and Adult High-Grade Glioma—Recent Advances

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