The tumor microenvironment (TME) plays a crucial role in the progression and treatment response of brain tumors, particularly gliomas and brain metastases. Friebel et al. conducted a single-cell analysis revealing that the TME is significantly shaped by tumor-specific leukocytes, indicating that the immune landscape is influenced by the tumor itself rather than solely by the central nervous system (CNS) milieu (ref: Friebel doi.org/10.1016/j.cell.2020.04.055/). Klemm et al. expanded on this by employing a comprehensive analysis of the immune cell composition in brain tumors, demonstrating that primary and metastatic tumors exhibit distinct immune profiles, which could inform therapeutic strategies (ref: Klemm doi.org/10.1016/j.cell.2020.05.007/). Furthermore, Vora et al. explored immunotherapeutic approaches targeting CD133+ cancer stem cells, which are implicated in tumor heterogeneity and treatment resistance, suggesting that targeting these cells could enhance therapeutic efficacy in glioblastoma (ref: Vora doi.org/10.1016/j.stem.2020.04.008/). These studies collectively underscore the complexity of the TME and its implications for developing targeted therapies in brain malignancies.

Molecular characterization of gliomas has revealed significant insights into their pathogenesis and potential therapeutic targets. Di Stefano et al. focused on FGFR3-TACC3 fusions, which occur in approximately 3% of gliomas, and characterized their clinical and radiological profiles, highlighting their prognostic significance (ref: Di Stefano doi.org/10.1093/neuonc/). Buccarelli et al. investigated the deregulated expression of the DLK1-DIO3 region in glioblastoma stem-like cells, identifying a tumor suppressor role for the long non-coding RNA MEG3, which may contribute to tumor aggressiveness (ref: Buccarelli doi.org/10.1093/neuonc/). Additionally, the CheckMate 143 trial by Reardon et al. compared nivolumab and bevacizumab in recurrent glioblastoma, revealing important data on overall survival outcomes that could influence treatment decisions (ref: Reardon doi.org/10.1001/jamaoncol.2020.1024/). These findings illustrate the intricate genetic landscape of gliomas and the ongoing efforts to translate molecular insights into clinical practice.

The development of effective therapeutic strategies for gliomas is challenged by drug resistance and the need for innovative approaches. Michealraj et al. highlighted the metabolic regulation of the epigenome in infantile ependymoma, demonstrating that hypoxic conditions can alter histone modifications, potentially driving tumor progression (ref: Michealraj doi.org/10.1016/j.cell.2020.04.047/). Rajesh et al. reported that lumefantrine, an antimalarial drug, can reverse radiation and temozolomide resistance in glioblastoma, suggesting a novel avenue for overcoming therapeutic challenges (ref: Rajesh doi.org/10.1073/pnas.1921531117/). Chen et al. investigated the expression of immune checkpoint molecules B7-H4 and PD-L1 in gliomas, finding that coexpression is rare, which may inform the development of combination immunotherapies (ref: Chen doi.org/10.1136/jitc-2019-000154/). Collectively, these studies emphasize the need for multifaceted approaches to address drug resistance and enhance treatment efficacy in gliomas.

Patient outcomes in neuro-oncology are significantly influenced by treatment strategies and their associated quality of life. Van der Meulen et al. evaluated health-related quality of life (HRQoL) in primary central nervous system lymphoma patients undergoing chemotherapy with or without rituximab, finding that the addition of rituximab did not adversely affect HRQoL over time (ref: van der Meulen doi.org/10.1016/j.annonc.2020.04.014/). Baroni et al. addressed the treatment gap in infant medulloblastoma, reporting on a regimen that avoids craniospinal irradiation while maintaining effective outcomes, thus reducing neurodevelopmental sequelae (ref: Baroni doi.org/10.1093/neuonc/). The CheckMate 143 trial also contributes to understanding treatment impacts on survival in glioblastoma, providing critical data for clinical decision-making (ref: Reardon doi.org/10.1001/jamaoncol.2020.1024/). These findings highlight the importance of balancing treatment efficacy with quality of life considerations in neuro-oncology.

Innovative imaging techniques and biomarker discovery are pivotal in enhancing the diagnosis and treatment of gliomas. Kim et al. explored the mechanisms of microRNA arm switching, identifying key regulators that could have implications for miRNA-based therapies (ref: Kim doi.org/10.1016/j.molcel.2020.04.030/). Vora et al. further contributed to this theme by developing CD133-targeting immunotherapies, which could serve as biomarkers for identifying cancer stem cells in glioblastoma (ref: Vora doi.org/10.1016/j.stem.2020.04.008/). Das et al. discussed the ethical considerations in neuro-oncology during the COVID-19 pandemic, emphasizing the need for a framework that balances patient care with resource allocation (ref: Das doi.org/10.1093/neuonc/). These studies collectively underscore the importance of integrating innovative imaging and biomarker research into clinical practice to improve patient outcomes.

Cancer stem cells (CSCs) and tumor heterogeneity are critical factors influencing glioma behavior and treatment response. Vora et al. highlighted the role of CD133+ CSCs in glioblastoma, demonstrating that targeting these cells with specific immunotherapies can potentially overcome treatment resistance and improve patient outcomes (ref: Vora doi.org/10.1016/j.stem.2020.04.008/). Buccarelli et al. investigated the DLK1-DIO3 region's deregulation in glioblastoma stem-like cells, revealing a tumor suppressor role for lncRNA MEG3, which may contribute to the aggressive nature of these tumors (ref: Buccarelli doi.org/10.1093/neuonc/). The CheckMate 143 trial by Reardon et al. also provides insights into the heterogeneity of treatment responses in recurrent glioblastoma, emphasizing the need for personalized therapeutic approaches (ref: Reardon doi.org/10.1001/jamaoncol.2020.1024/). These findings illustrate the complex interplay between CSCs and tumor heterogeneity, underscoring the necessity for targeted therapies in glioma management.

The ethical considerations in neuro-oncology have gained prominence, particularly in light of the COVID-19 pandemic. Das et al. reflected on the ethical dilemmas faced by healthcare providers, emphasizing the need to balance patient care with resource allocation during crises (ref: Das doi.org/10.1093/neuonc/). This discussion is crucial as it highlights the complexities of decision-making in neuro-oncology, where treatment options must be weighed against the potential impact on healthcare resources. The integration of ethical frameworks into clinical practice is essential for guiding treatment decisions and ensuring equitable patient care. As neuro-oncology continues to evolve, addressing these ethical challenges will be vital for improving patient outcomes and maintaining the integrity of healthcare systems.