搜索结果：Neuro-oncology advances

Glioblastoma (GBM) is the most aggressive primary brain tumor in adults and is characterized by rapid progression, marked spatial and molecular heterogeneity, and poor prognosis despite multimodal treatment strategies. Tumor behavior is not determined solely by intrinsic genetic alterations but also by dynamic interactions within the tumor microenvironment, including hypoxia, aberrant angiogenesis, immune modulation, and metabolic reprogramming, which are major drivers of treatment resistance and disease recurrence. Magnetic resonance imaging (MRI) remains the cornerstone of diagnosis and treatment planning; advanced quantitative techniques have expanded its role beyond structural assessment, enabling in vivo characterization of tissue cellularity, vascular architecture, perfusion, and microenvironmental dynamics. Positron Emission Tomography (PET) provides complementary metabolic and molecular information, improving tumor delineation, detection of infiltrative disease, and assessment of hypoxia and treatment response. PET-MRI integration within a multimodal framework enables spatially resolved mapping of tumor heterogeneity and microenvironmental niches that cannot be adequately assessed by either modality alone. Radiomics and radiogenomics approaches further enhance this paradigm by extracting quantitative imaging features that reflect underlying biological processes and linking imaging phenotypes with molecular and clinical outcomes. Artificial Intelligence enables automated feature extraction, multimodal data integration, and predictive modeling for diagnosis, prognosis, and treatment response assessment. Despite these advances, clinical translation remains limited by methodological heterogeneity, lack of standardized acquisition protocols, and insufficient prospective validation. Future research should prioritize harmonized multicenter studies and biologically informed multimodal analytical frameworks to enable the routine implementation of microenvironment-oriented precision imaging in GBM management.

World Health Organization (WHO) grade 2 and 3 meningiomas are aggressive neoplasms characterized by high postoperative recurrence rates and unfavorable prognoses. Despite advances in surgical and radiotherapeutic management, effective systemic treatment options for recurrent WHO grade 2/3 meningiomas remain limited, with most therapies still under clinical investigation. To evaluate the efficacy and safety of various pharmacological treatment strategies for recurrent high-grade meningioma, including conventional chemotherapy, targeted therapy, and immunotherapy. A comprehensive literature search was conducted in PubMed, Embase, Web of Science, and ClinicalTrials.gov from database inception to August 2025. Relevant studies investigating conventional chemotherapy, targeted therapy, and immunotherapy for recurrent high-grade meningioma were systematically reviewed to summarize current advances in precision therapeutic strategies. Conventional cytotoxic chemotherapy has demonstrated limited survival benefit in recurrent high-grade meningioma and is primarily used for palliative symptom management. In contrast, molecular targeted therapies have shown varying degrees of anti-tumor activity, including anti-angiogenic agents, Tyrosine Kinase Inhibitors (TKI), Focal Adhesion Kinase (FAK) inhibitors, and Mammalian Target of Rapamycin (mTOR) inhibitors. Among these, Bevacizumab demonstrated relatively favorable efficacy, prolonging median progression-free survival to 12-18 months in phase II clinical studies. Immunotherapy has also emerged as a promising therapeutic approach. Programmed death-1 (PD-1) inhibitors achieved 6-month progression-free survival rates (PFS-6) of up to 48% in early clinical studies. Furthermore, emerging immunotherapeutic strategies, such as chimeric antigen receptor T-cell (CAR-T) therapy, oncolytic virus (OVs) therapy, and personalized tumor vaccines, have demonstrated preliminary therapeutic potential. Nevertheless, developing standardized treatment strategies remains challenging due to limited clinical trial sample sizes, methodological heterogeneity, and substantial intertumoral and intratumoral molecular variability. Future research should prioritize molecular subtype-based therapeutic strategies to facilitate personalized treatment according to tumor biology. In addition, combination regimens integrating targeted therapy and immunotherapy may further improve therapeutic response and quality of life in patients with recurrent high-grade meningioma.

Intracranial germ cell tumors (IGCTs) are a group of malignant central nervous system (CNS) tumors primarily affecting children and adolescents, whose pathogenesis remains incompletely understood. The embryonic cell theory suggests that IGCTs may originate from pluripotent embryonic cells that escape normal migration and differentiation during embryonic development. Research indicates that DNA hypomethylation, abnormalities in the MAPK and/or PI3K signaling pathways, and chromosomal abnormalities play significant roles in the development and progression of IGCTs. Diagnosis relies on a comprehensive evaluation of clinical presentation, tumor markers, and imaging studies, ultimately confirmed by histopathology. In recent years, novel biomarkers in serum and cerebrospinal fluid, such as microRNAs (miRNAs) and circulating tumor DNA (ctDNA), have gained increasing attention for their diagnostic and prognostic value. Current treatment predominantly relies on surgery, radiotherapy, and chemotherapy, though the optimal radiation field and dose remain controversial. With a deepening understanding of molecular drivers and the tumor microenvironment, targeted therapy and immunotherapy are gradually being applied clinically. As the survival rate of patients with IGCTs improves, we are also confronted with new clinical challenges: how to minimize treatment-related long-term sequelae while maintaining excellent therapeutic outcomes, and improve the prognosis for refractory non-germinomatous germ cell tumors (NGGCTs). This review summarizes recent advances in genetic variation, diagnosis, and treatment of IGCTs, serving as a reference for exploring personalized therapeutic strategies, reducing treatment-related toxicity, and improving long-term prognosis.

Diffuse gliomas remain among the most surgically challenging tumors, characterized by their infiltrative nature, proximity to eloquent brain structures, and the formidable barrier posed by the BBB to systemic therapeutic delivery. Maximizing extent of resection (EOR) while preserving neurological function remains a central determinant of survival and quality of life, and the iterative integration of intraoperative technologies into surgical practice has become essential to achieving this balance. We performed a comprehensive narrative review of established and emerging intraoperative technologies for glioma surgery, organized around two clinical imperatives: optimizing tumor delineation and safe resection, and enhancing local therapeutic delivery. Awake craniotomy with direct electrical stimulation remains the gold standard for preserving eloquent cortex and subcortical tracts, consistently reducing postoperative neurological deficits while increasing gross total resection rates. Fluorescence-guided surgery with 5-ALA and fluorescein enhances real-time tumor margin visualization, and their combined use achieves greater EOR than either agent alone. Intraoperative MRI compensates for progressive brain shift and, when used alongside 5-ALA, provides the strongest currently available platform for maximizing safe resection. Augmented reality navigation further enhances spatial orientation by overlaying 3D virtual anatomy directly onto the operative field. Emerging tissue characterization tools, including stimulated Raman histology, confocal laser endomicroscopy, and AI-based platforms such as FastGlioma and DeepGlioma, enable rapid intraoperative molecular diagnosis without the delays of conventional frozen section pathology. For therapeutic delivery, low-frequency focused ultrasound and convection-enhanced delivery bypass the BBB to achieve high local drug concentrations, while endovascular intra-arterial infusion enables targeted delivery across the tumor vascular territory. Photodynamic and sonodynamic therapy generate localized cytotoxic effects within the resection cavity at the time of surgery. Intraoperative brachytherapy with Cesium-131 tile implants delivers conformal radiation at the time of resection and may potentiate antitumor immunity. Laser interstitial thermal therapy combines cytoreduction with sustained BBB disruption, creating a therapeutic window for otherwise CNS-impermeant agents including checkpoint inhibitors. The deliberate integration of these complementary modalities into a phase-organized intraoperative workflow, spanning preoperative planning, real-time resection guidance, intraoperative margin and tissue assessment, and post-resection locoregional therapeutic delivery, defines the emerging paradigm of precision glioma surgery. Realizing the full potential of this framework will require prospective validation of combinatorial strategies, standardization of technology integration protocols, and rigorous evaluation of neurological and oncological outcomes.

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Brain tumors remain among the most lethal cancers, largely due to their remarkable heterogeneity, plasticity, and resistance to therapy. The second Brain Tumor Meeting by the Sea (Saint-Malo, France, 2026) brought together researchers, clinicians, and patient representatives to discuss emerging concepts shaping the future of neuro-oncology. A recurring theme was the shift from a tumor-centric perspective toward an ecosystem-based view that integrates tumor cells, microenvironmental cues, developmental context, and patient-centered dimensions. Advances in patient-derived models, multi-omics approaches, spatial technologies, and artificial intelligence are refining tumor classification and revealing novel therapeutic vulnerabilities. Discussions highlighted cellular plasticity and stress-adaptation mechanisms as key drivers of tumor evolution and treatment resistance. They also emphasized the need for identifying dynamic biomarkers and developing more physiologically relevant disease models. Beyond biological discoveries, the meeting underscored the importance of strengthening interactions among research, clinical care, and patient communities. Together, these advances support a more integrated framework for understanding brain tumors and developing future therapeutic strategies.

Glioblastoma (GBM) is one of the most aggressive and lethal primary brain tumors in adults, characterized by dynamic clonal evolution and extensive genomic, cellular, spatial, and microenvironmental heterogeneity. Multi-omics studies have revealed that GBM follows complex evolutionary trajectories involving genetic, epigenetic, transcriptional, and immune-microenvironmental remodeling as tumors grow, adapt to the brain microenvironment, and acquire therapeutic resistance. Increasing evidence suggests that GBM may originate from aberrant neural stem or progenitor cells, including those residing in the subventricular zone, and that glioblastoma stem cells (GSCs) contribute to tumor propagation, heterogeneity, and recurrence. A key conceptual challenge is to reconcile hierarchical cancer stem cell models, in which GSCs are viewed as relatively stable tumor-propagating subpopulations, with dynamic state plasticity models, in which stem-like properties can be reversibly acquired or lost during transitions among proneural-like, mesenchymal-like, invasive, and therapy-tolerant states. Recent advances in single-cell profiling, spatial transcriptomics, lineage tracing, organoid culture, 3D bioprinting, genetically engineered models, and artificial intelligence (AI)-assisted computational modeling have substantially improved the ability to study these processes. However, no currently available model fully recapitulates human GBM heterogeneity, recurrence, treatment history, and tumor-microenvironment interactions. Therefore, model selection should be guided by clearly defined mechanistic questions rather than by reliance on any single platform. This review summarizes current advances in in vitro, ex vivo, in vivo, and computational models for studying GBM evolution and heterogeneity, and discusses how integrated model pipelines may improve preclinical drug testing, treatment-response prediction, and precision neuro-oncology.

Radiometal-based radiopharmaceuticals have become central to the advancement of molecular imaging and targeted radionuclide therapy, offering powerful tools for the diagnosis and treatment of diseases affecting the brain. The unique chemical versatility of radiometals - encompassing a broad range of coordination chemistries, physical half-lives, and emission properties - combined with an expanding repertoire of targeting biomolecules enables highly tunable and increasingly modular imaging and therapeutic platforms. In particular, positron emission tomography (PET) using radiometal-labelled tracers provides sensitive, quantitative, and non-invasive assessment of molecular processes in vivo, while radiometal-based therapeutic agents enable the selective delivery of cytotoxic radiation to diseased tissue. This review examines recent progress in the application of radiometal-based radiopharmaceuticals for brain disorders, with a focus on neuro-oncology - including primary brain tumours and brain metastases - as well as neurodegenerative diseases such as Alzheimer's disease and Parkinsons disease. Key challenges unique to brain applications are discussed, including the restrictive nature of the blood-brain barrier, heterogeneous target expression, and off-target biodistribution. Recent advances in chelator development, emerging antigen targets, alternative routes of administration, and strategies to improve brain delivery are highlighted. While imaging agents continue to lead therapeutic development in this space, reflecting the need for accurate disease characterisation, recent progress underscores the potential of radiometal-based therapies for brain disease. In particular, immunoPET has emerged as a powerful tool for evaluating target expression, biodistribution, and treatment response. Collectively, these developments position radiometal-based radiopharmaceuticals as a promising and evolving platform enabling personalised treatment strategies for neurological disorders.

Proton beam therapy (PBT) is increasingly used in paediatric neuro-oncology due to its favourable dose distribution and potential to reduce treatment toxicity. As its clinical use expands, neuroradiologists play a central role in recognising therapy-related changes and supporting long-term surveillance. This review outlines key neuroradiological considerations across the PBT pathway. MRI is fundamental to planning, but its integration requires modified workflows, specialised immobilisation equipment, and tailored sequence design to balance geometric accuracy, signal-to-noise constraints, and patient tolerability. Ongoing sequence optimisation-including the use of high-resolution isotropic volumes and advanced reconstructions-aims to improve delineation of target structures and organs at risk. During treatment, anatomical changes such as tumour or cyst evolution may alter proton range, necessitating interval imaging and, in selected cases, adaptive replanning. Post-treatment assessment presents further challenges, as PBT may produce distinct radiological appearances compared with photon therapy. These include patterns of pseudoprogression, variations in white matter and microvascular injury, and a spectrum of vascular complications. Accurate interpretation is essential to distinguish treatment effects from recurrence and to guide further management. Advances in MRI-only workflow development, synthetic CT generation, ultra-high-field imaging, and computational modelling offer opportunities to further improve treatment precision and refine the characterisation of post-treatment effects. As PBT becomes more widely delivered, this review will aid neuroradiologists at referring centres who will increasingly encounter its distinct post-treatment appearances, highlighting the importance of familiarity with these patterns in routine practice and aiding standardisation of post-treatment imaging protocols.

Glioblastoma almost invariably recurs at the margin of the resection cavity despite maximal treatment combining surgery, external beam radiotherapy, and chemotherapy. More than 80% of recurrences arise locally, underscoring a persistent unmet need for improved locoregional control. Despite major advances in conformal external beam radiotherapy techniques, durable local control remains challenging because of diffuse tumor infiltration, biological resistance, and the need to preserve surrounding healthy brain tissue. Although internal radiotherapy has existed for decades and is supported by a compelling radiobiological rationale, its integration into routine neuro-oncological practice remains limited. In this narrative review, we examine why a technically established approach, based on a sound biological rationale, continues to play a limited role in glioblastoma management. We focus on dosimetric standardization as a major challenge specific to internal radiotherapy. Unlike external beam radiotherapy, which prescribes absorbed dose within a standardized planning framework, internal radiotherapy delivers radioactive activity, resulting in spatially and temporally evolving dose distributions that are difficult to reconstruct, compare, and biologically interpret. Recent advances in intracavitary implantable and injectable platforms, patient-specific modeling, and improved understanding of glioblastoma radiobiology may enable a shift toward biologically informed treatment planning. By integrating radiation physics, tumor biology, and clinical decision-making, modern brachytherapy may emerge as a structured complement to multimodal glioblastoma care aimed at achieving improved local control.

Glioblastoma (GBM) remains the most aggressive primary brain tumor in adults, characterized by inevitable recurrence, extensive inter-and intratumoral heterogeneity, and resistance to current therapies. A defining feature of GBM is the dynamic interplay between malignant cells and a diverse tumor microenvironment (TME), which together drive disease progression, therapeutic adaptation, and relapse. Understanding these complex cellular ecosystems has therefore become a major focus of glioblastoma research. Recent advances in spatial omics technologies have transformed our ability to investigate GBM biology directly within intact tissue architectures. Over the past five years, an expanding array of spatial transcriptomic, proteomic, and multi-omic platforms has enabled high-dimensional characterization of cellular states, cell-cell interactions, and tissue niches while preserving spatial context. These approaches have generated unprecedented insights into tumor organization, cellular plasticity, immune landscapes, vascular niches, and treatment-induced ecosystem remodeling. In this review, we provide an overview of spatial omics applications in glioblastoma research so far. We summarize the technologies employed, the types and numbers of patient samples analyzed, and the major biological and clinical insights generated. We compare the strengths and limitations of different spatial platforms, discuss key considerations for study design and data interpretation, and highlight emerging trends in multimodal and longitudinal analyses. By integrating both technological and biological perspectives, this review serves as a practical resource for researchers seeking to implement spatial omics approaches in glioblastoma studies and to advance precision neuro-oncology.

White matter (WM) tract involvement represents a critical determinant of functional outcome in neuro-oncology. Although substantial advances in diffusion tensor imaging (DTI) and intraoperative mapping have improved characterization of WM organization, the relationship between microstructural integrity and morphometric alterations of associative fasciculi in different tumor histotypes remains incompletely understood. We investigated the association between fractional anisotropy (FA), volumetric and length parameters of the inferior fronto-occipital fasciculus (IFOF) and arcuate fasciculus (AF) across distinct intracranial tumor types. In this multicenter retrospective study, 156 patients undergoing surgery for brain tumors were included. All lesions were located in proximity to the IFOF or AF and underwent preoperative deterministic tractography based on standardized DTI protocols. Linear mixed-effects models, adjusted for relevant covariates, assessed the association between FA and tract morphometry, including interaction terms for tumor type and hemisphere. Higher FA was strongly associated with both AF and IFOF tract volume (adjusted p&#x2009;<&#x2009;0.001), whereas associations with tract length were weaker and not consistently significant. The association between FA and IFOF volume appeared stronger in gliomas than in metastases or meningiomas, suggesting potential histotype-related difference in WM involvement. The healthy hemisphere showed higher FA and morphometric measures than the tumor-affected side. FA was significantly associated with morphometric features of WM tract, particularly in infiltrative tumors. Integrating FA into preoperative assessment may enhance surgical planning and support strategies aimed at preserving functional connectivity.

Glioblastoma remains the most aggressive primary malignant brain tumor in adults, with survival largely unchanged despite advances in molecular diagnostics and supportive care. Therapeutic failure reflects fundamental biological and anatomical barriers, including intratumoral heterogeneity, an immunosuppressive tumor microenvironment, and restricted drug delivery across the blood-brain barrier. In this Review, we summarize the current standard of care and critically examine emerging strategies aimed at overcoming these constraints, including locoregional delivery technologies, immunotherapy, biomarker-defined precision approaches, and adaptive clinical trial designs. We highlight key translational and clinical studies shaping the field and discuss principles for developing more effective, integrated therapeutic paradigms.

The mammalian polyamines (putrescine, spermidine and spermine) are ubiquitous polycations, long recognized for their indispensable roles in maintaining cell proliferation, differentiation and survival. Traditionally viewed as metabolic supporters of growth, polyamines have recently emerged as active regulators of cell-cell signaling in diverse physiological and pathological settings. Through intercellular polyamine transfer, modulation of ion channels and interactions with cell-surface receptors, polyamines orchestrate intricate signaling networks, from neurotransmission in the nervous system to cytokine signaling in the immune compartment. Many cancers, though most clearly, central nervous systems (CNS) cancers, exploit neuro- and immunomodulatory circuits, effectively hijacking neural and immune signaling pathways to sustain growth and evade surveillance. Thus, an integrated, multi-disciplinary perspective is required to overcome hurdles in the treatment of these aggressive malignancies. In light of ongoing clinical trials aimed at disrupting polyamine synthesis and transport in brain tumors, better defining the role of polyamines in mediating tumor-host interactions is essential for maximizing anti-tumor efficacy while minimizing normal tissue toxicity. This review integrates advances from cancer biology, immunology and neuroscience to comprehensively discuss the mechanisms through which polyamines regulate cell-cell signaling, the role of these pathways in brain tumor progression and the diagnostic and therapeutic opportunities that arise from this knowledge.

Pediatric solid high-risk malignancies mostly lack established molecular biomarkers for early detection, minimal residual disease assessment, or treatment monitoring. Challenges include small patient numbers, limited sample volumes, low tumor mutational burden, and few recurrent alterations. Within the multicenter pediatric precision oncology program INFORM, we prospectively collected liquid biopsies from 130 pediatric patients and optimized cell-free DNA isolation and analysis. Whole-genome, whole-exome, and targeted panel sequencing were performed using liquid biopsy-adapted protocols. Integrating tissue-derived molecular profiles and orthogonal validation revealed that low-coverage whole-genome sequencing reliably detects circulating tumor DNA. An in silico ctDNA estimation score, combining fragment length and genome segment alterations, improved sensitivity and specificity to 95%, enabling plasma-based tumor detection in 93% of patients. Whole-exome and panel sequencing effectively identified clinically relevant, potentially druggable molecular targets. However, their utility varied substantially across different tumor entities, underscoring the need for entity-specific considerations in the interpretation and application of these methodologies. In-depth analyses demonstrated liquid biopsy's potential to track tumor evolution, identifying common tumor ancestors and refining patient stratification. This study advances liquid biopsy methodologies in pediatric oncology and provides a rationale that, as SNVs are more sensitively captured by panel sequencing and WES, while CNVs are better represented by lcWGS and WES. The underlying tumor genomic profile should guide the selection of liquid biopsy assays to optimize clinical decision-making. Systematic liquid biopsy analyses within the pediatric precision oncology INFORM registry enabled a real-world, multicenter comparison of sequencing approaches across high-risk malignancies. By optimizing preanalytical and bioinformatic tools for pediatric settings, we improved plasma-based cancer detection, molecular tumor characterization, and identification of targetable alterations, laying the groundwork for integration into personalized medicine programs and clinical trials.

Posterior fossa tumours present substantial clinical challenges due to their deep anatomical location and proximity to vital neurovascular structures. Limited awareness and diagnostic delays remain major obstacles to early detection of paediatric brain tumours. For the last two decades, the 5-year overall&#xa0;and event-free survival of children with posterior fossa tumours has been doubled due to the improvement in the diagnostic tools and the advances in the surgical techniques approaching total or near-total resection. This retrospective comparative cohort study was conducted at a tertiary care cancer hospital in Pakistan, following approval from the Institutional Review Board (IRB). The study included paediatric patients with posterior fossa tumours treated between January 2021 and February 2025 and compared two cohorts: the Regular Pathway and the Rapid Assessment Pathway (RAPT). Collected variables included demographic characteristics, duration of symptoms, time interval from initial symptom onset to acceptance for treatment (from walk-in clinic), surgical intervention, frequency of shunt or external ventricular drain insertion and initiation of adjuvant therapy. Data were analysed using SPSS version 27. A total of 59 patients were included, 30 patients in the Regular Pathway (January 2021-December 2023) and 29 patients in RAPT (January 2024-February 25). &#xa0;In the Regular Pathway, the mean duration of acceptance after initial presentation was 15 days, as compared to RAPT, which was 5 days (p &#x2264; 0.001). The frequency of shunt insertion was reduced significantly in RAPT compared to Regular Pathways. A total of 83% of patients in RAPT were operated within 72 h of acceptance as compared to Regular Pathway cohorts, in which 55% patients had surgery within 4 weeks (p &#x2264; 0.001). The average duration of the start of adjuvant therapy in the RAPT cohort was within 6 weeks, while in the Regular Pathway cohort, it was 7 weeks. RapidRAPT has demonstrated a significant improvement in the timeliness of care for paediatric patients diagnosed with posterior fossa tumours. Early intervention facilitated by RAPT contributes to better outcomes and reduced treatment delays.

Brain metastases from breast cancer (BCBMs) are a major cause of morbidity and mortality and remain a critical unmet clinical need across molecular subtypes. Their incidence is rising as improved systemic therapies prolong survival in metastatic breast cancer and advances in neuroimaging allow earlier detection of central nervous system (CNS) disease. Historically, management relied mainly on local approaches such as surgery and radiotherapy because many systemic agents have limited ability to cross the blood-brain barrier. However, the therapeutic landscape is rapidly evolving with the development of systemic treatments showing clinically meaningful intracranial activity. In hormone receptor-positive/HER2-negative disease, treatment options are expanding with targeted and novel endocrine-based therapies that may achieve therapeutically relevant CNS concentrations. In addition, targeting the PI3K/AKT/mTOR pathway and the increasing use of antibody-drug conjugates (ADCs), including trastuzumab deruxtecan in HER2-low and-ultralow disease, may further broaden systemic strategies. In HER2-positive breast cancer, brain-penetrant tyrosine kinase inhibitors and highly active ADCs have significantly improved outcomes. Tucatinib-based combinations and trastuzumab deruxtecan have demonstrated substantial intracranial activity in prospective trials, shifting the treatment paradigm by supporting systemic therapy even in the presence of active brain metastases. Lastly, in triple-negative breast cancer, outcomes remain poor, but ADCs, immunotherapy-based strategies, and PARP inhibitors for germline BRCA-mutated disease are under investigation. A major limitation remains the underrepresentation of patients with brain metastases in clinical trials. This review summarizes current evidence on systemic therapies for BCBM across subtypes and highlights the need for CNS-inclusive trials and the development of effective CNS-active treatments.

Despite advances in precision oncology, effective personalized treatments are still lacking for most patients with cancer1. The Cancer Dependency Map (DepMap) accelerates this field by systematically identifying cancer vulnerabilities in diverse preclinical models. Data from over 1,300 cell lines have led to the discovery of new therapeutic strategies across multiple tumour types2. However, mapping cancer vulnerabilities using traditional cell lines has limitations, including insufficient cancer subtype representation and the impact of culture conditions on perturbation responses. Here we perform 147 genome-scale CRISPR screens and multi-omic characterizations of next-generation (NextGen) cancer models (organoids and spheroids) across 10 cancer types. This strategy enables the expansion of DepMap to cover new genomic and molecular subtypes and to identify new biomarker-associated vulnerabilities. These new models also preserve transcriptional programs that are&#xa0;silenced in traditional cell lines and facilitate the discovery of specific gene dependencies associated with these programs. Comparisons of traditional and NextGen cancer models enable further identification of distinct effects of growth format and culture medium on gene essentiality. The integrated dataset combines data from both model types to offer a valuable, expansive resource for exploring cancer vulnerabilities and is accessible via the DepMap portal.

Metal ions are key regulators of the neuro-immune-tumor axis. Recent studies provide concrete evidence that neuronal Ca2+ pulses drive tumor-neuron integration and shape immune signaling. Synaptic Zn2+ and ZIP transporters modulate synaptic transmission and tumor growth. Tumor iron accumulation fuels proliferation while creating a clear ferroptosis vulnerability. Copper promotes angiogenesis, lysyl oxidase (LOX)-mediated extracellular matrix (ECM) remodeling and metastasis, and implicates cuproptosis as a therapeutic target. Mn potentiates cyclic GMP-AMP synthase (cGAS)-STING signaling and serves as both an immune adjuvant and manganese-enhanced magnetic resonance imaging (MEMRI) contrast. Besides, Mg and K+ regulate kinase/T-cell receptor (TCR) function and tumor-neuron excitability, respectively. Despite these advances, major gaps persist, notably limited spatial and temporal mapping of labile metal pools, a paucity of cell-type-specific causal perturbations, and underdeveloped tumor-targeted metal-modulating therapies with proven safety. We therefore propose a focused research agenda: integrate spatial metallomics with single-cell multiomics, deploy metal-sensitive longitudinal imaging, apply conditional genetic and chemogenetic perturbations and organotypic models to dissect neuro-immune cross-talk, and implement preclinical pipelines emphasizing tumor-selective delivery and comprehensive safety testing.