Sex Differences in Adult Glioblastoma and Paediatric-type High-Grade Gliomas: Biology, Therapeutic Response, and Resistance Mechanisms

High-grade gliomas remain among the most aggressive primary brain tumors. In adults, glioblastoma (GBM, IDH-wildtype) dominates, whereas paediatric-type diffuse high-grade gliomas — including diffuse midline glioma (H3 K27-altered) and diffuse hemispheric glioma (H3 G34-mutant) — represent distinct, molecularly defined entities. Across both groups, tumors exhibit marked heterogeneity in disease progression, treatment response, and patient outcomes. Emerging evidence suggests that biological sex significantly influences their incidence, tumor microenvironment, immune regulation, metabolic reprogramming, therapeutic efficacy, and mechanisms of resistance. However, sex-specific molecular pathways and their translational implications remain insufficiently understood.

This Research Topic aims to highlight recent advances in understanding the role of sex as a biological variable in high-grade glioma research, spanning both adult glioblastoma and paediatric-type high-grade gliomas. We welcome original research articles, reviews, and perspectives addressing sex-dependent differences in tumor biology. We welcome original research articles, reviews, and perspectives addressing sex-dependent differences in tumor biology, genomic and epigenomic regulation, cancer stem cell behavior, immune responses, metabolic adaptations, treatment sensitivity, and resistance to standard and emerging therapies. Studies utilizing preclinical models, clinical datasets, multi-omics approaches, artificial intelligence, and precision medicine strategies are particularly encouraged. We aim to advance mechanistic insights into sex-specific determinants of glioblastoma progression and therapeutic response, ultimately facilitating the development of more personalized and effective treatment strategies for patients with GBM.

We invite submissions addressing, but not limited to, the following themes:

• Sex-specific molecular, genetic, and epigenetic mechanisms driving glioblastoma initiation and progression
• Biological differences in glioblastoma stem cells, tumor heterogeneity, and cellular plasticity between males and females
• Sex-dependent interactions within the glioblastoma tumor microenvironment, including immune and stromal components
• Influence of sex hormones and hormone-related signaling pathways on glioblastoma growth and invasion
• Sex differences in metabolism, mitochondrial function, and therapeutic vulnerabilities in GBM
• Mechanisms underlying differential responses to chemotherapy, radiotherapy, immunotherapy, and targeted therapies
• Sex-specific pathways contributing to treatment resistance, tumor recurrence, and disease progression
• Application of multi-omics, artificial intelligence, and precision medicine approaches to identify sex-informed biomarkers and therapeutic strategies
• Clinical studies evaluating sex-based differences in patient outcomes, prognosis, and treatment efficacy
• Emerging therapeutic interventions aimed at overcoming sex-specific resistance mechanisms in glioblastoma
• Sex-specific biology, therapeutic response, and resistance in paediatric-type high-grade gliomas, including diffuse midline glioma (H3 K27-altered) and diffuse hemispheric glioma (H3 G34-mutant)
• Comparative analyses of sex-related differences between adult glioblastoma and paediatric high-grade gliomas



Please note that manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases that are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of the scope of this Research Topic.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Case Report
• Clinical Trial
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• ... View all formats

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Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Case Report
• Clinical Trial
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Systematic Review
• Technology and Code

Keywords: Therapeutic Response, Glioblastoma, Sex Differences, Mechanisms

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.