Purpose of review Cancer neuroscience has evolved from a predominantly preclinical, mechanistic discipline into a clinically relevant framework for understanding and treating patients with brain malignancies. This review synthesizes recent advances across glioblastoma (GBM), diffuse midline glioma (DMG), and brain metastases, with particular emphasis on identifying circuit-level, neurotransmitter-mediated, electrophysiologic, and network properties that are emerging as clinically actionable biomarkers and therapeutic targets. Recent findings Human connectomics and retrograde tracing studies demonstrate that GBM integrates into distributed, brain-wide neural circuits. In DMG, neuron-tumor signaling has expanded beyond glutamatergic mechanisms to include GABAergic and cholinergic neurotransmission, while patterns of neural connectivity have been associated with regional immunosuppression and patient survival. Patch-seq and electrophysiologic profiling have identified distinct functional states of malignant cells, and spatial transcriptomic analyses have linked malignant cell plasticity to neuron-rich invasive niches. Although these discoveries are driving the development of neurophysiologic biomarkers and circuit-directed therapeutic strategies, they have not yet translated into clinical practice. Emerging cellular atlases and mechanistic studies of small cell lung cancer and brain metastases further suggest that neural circuit integration is a broader feature of cancer biology rather than a phenomenon restricted to gliomas. Summary The field's critical next step is to integrate cancer neuroscience-directed therapeutic strategies with prospectively validated, multimodal biomarkers that account for age and disease-specific neurobiology and reliably distinguish tumor associated states from physiologic aging and adaptive changes within the peritumoral microenvironment.
Purpose of review Glioblastoma is the most aggressive and treatment-resistant primary brain tumor in adults. Given its clinical severity and biological complexity, research efforts are focused on understanding and targeting intratumoral heterogeneity, adaptive resistance, drug delivery barriers, and the immunosuppressive tumor microenvironment. This review highlights emerging therapeutic approaches for the treatment of glioblastoma including advances in radiation planning, molecularly targeted therapy, immunotherapy, blood-brain barrier modulation, and neuronal signaling. Recent findings Radiation therapy remains a cornerstone of glioblastoma treatment, and advances in image-guided planning are being developed to refine treatment margins and improve tolerability without compromising efficacy. Blood–brain barrier permeability is being improved through device-assisted approaches, including focused ultrasound in combination with systemic therapies. Molecularly targeted and immunotherapeutic approaches continue to be evaluated, increasingly with biomarker-informed strategies to optimize patient selection. In parallel, drug repurposing, neuronal modulation, and metabolic interventions have shown promising preclinical and retrospective signals and are moving towards prospective studies. Interventions to improve quality of life are also underway with early palliative care showing significant impact for patients with glioblastoma. Summary As the field moves towards tailored and precision-guided approaches, combination strategies remain central to addressing the multiple mechanisms by which glioblastoma evades treatment.
Purpose of review Discoveries relating to the cancer neuroscience of gliomas have reframed brain tumor-related epilepsy (BTRE) as the product of reciprocal interactions at the neural–tumor interface. This framework provides the rationale for targeted strategies to optimize both seizure control and brain tumor survival outcomes. Recent findings Feedforward dynamics involving hyperexcitability and cellular proliferation in glioma-infiltrated cortex drive synaptic remodeling of neural circuits that correlate with shorter survival. Seizure assessment metrics demonstrate that worsening seizure control may precede or align with progressive disease. In this context, early evidence indicates a potential role for targeted tumor-directed therapy in addition to antiseizure medications (ASMs) for optimizing seizure control. Noncontrolled studies evaluating ASM tapering strategies in BTRE suggest that tumor stability is more important for seizure control than the duration of seizure freedom. Summary BTRE involves dynamic and fluctuating seizure risk driven by tumor biology, tumor-directed therapy, and treatment response. Hyperexcitability at the cellular level and clinical seizure activity are increasingly understood as a reflection of tumor biology and a potentially modifiable target to improve outcomes. The addition of seizure assessments as secondary endpoints in brain tumor clinical trials may lead to a refined individualized and disease-specific approach to ASM management.
PURPOSE OF REVIEW:Inclusion body myositis (IBM) is the most prevalent acquired myopathy in adults over 50 years of age, yet effective disease-modifying therapy has remained elusive. The longstanding debate over whether degeneration or inflammation is the primary driver has now given way to a model of bidirectional interplay. This review critically appraises advances published between January 2025 and June 2026, encompassing molecular pathomechanisms, early diagnostic strategies, disease-modifying therapies, and rehabilitation. RECENT FINDINGS:A pivotal mechanistic advance is the demonstration that TDP-43 nuclear depletion in IBM myonuclei generates cryptic exon-derived neoantigens that directly activate CD8 + T cells, molecularly unifying cell-autonomous degeneration and adaptive immune activation. In parallel, mitochondrial DNA leakage activates the cGAS-STING innate immune pathway prior to T cell infiltration. An endogenous compensatory mechanism involving the NORAD-Pumilio regulatory axis has also been identified. Clinically, preliminary data from the Phase 2/3 MUSCLE trial suggest a potential 50% slowing of progression in mild-to-moderate IBM with the anti-KLRG1 antibody ulviprubart, pending full peer-reviewed publication, while novel diagnostic and rehabilitation strategies further advance personalized care. SUMMARY:A molecular cascade from cell-autonomous TDP-43 dysfunction to cryptic epitope-driven immune activation could underlie the pathogenesis of IBM. Personalized multidisciplinary care integrating early diagnosis, targeted disease-modifying therapy, and advanced rehabilitation represents the emerging treatment paradigm.
