Differentiating Glioma Recurrence and Pseudoprogression by APTw CEST MRI.

Objectives: Recurrent glioma is highly treatment resistant due to its metabolic, cellular, and molecular heterogeneity and invasiveness. Tumor monitoring by conventional MRI has shortcomings to assess these key glioma characteristics. Recent studies introduced chemical exchange saturation transfer for metabolic imaging in oncology and assessed its diagnostic value for newly diagnosed glioma.

Spatio-temporal transcriptomics of chromothriptic SHH-medulloblastoma identifies multiple genetic clones that resist treatment and drive relapse.

Paediatric medulloblastomas with chromothripsis are characterised by high genomic instability and are among the tumours with the worst prognosis. However, the molecular makeup and the determinants of the aggressiveness of chromothriptic medulloblastoma are not well understood. Here, we apply spatial transcriptomics to profile a cohort of 13 chromothriptic and non-chromothriptic medulloblastomas from the same molecular subgroup.

Assessment of Tumor Cell Invasion and Radiotherapy Response in Experimental Glioma by Magnetic Resonance Elastography.

Background: Gliomas are highly invasive brain neoplasms. MRI is the most important tool to diagnose and monitor glioma but has shortcomings. In particular, the assessment of tumor cell invasion is insufficient.

Next Directions in the Neuroscience of Cancers Arising outside the CNS.

The field of cancer neuroscience has begun to define the contributions of nerves to cancer initiation and progression; here, we highlight the future directions of basic and translational cancer neuroscience for malignancies arising outside of the central nervous system.

Embracing cancer complexity: Hallmarks of systemic disease.

The last 50 years have witnessed extraordinary developments in understanding mechanisms of carcinogenesis, synthesized as the hallmarks of cancer. Despite this logical framework, our understanding of the molecular basis of systemic manifestations and the underlying causes of cancer-related death remains incomplete. Looking forward, elucidating how tumors interact with distant organs and how multifaceted environmental and physiological parameters impinge on tumors and their hosts will be crucial for advances in preventing and more effectively treating human cancers.

Tunneling nanotubes and tumor microtubes-Emerging data on their roles in intercellular communication and pathophysiology: Summary of an International FASEB Catalyst Conference October 2023.

In the past decade, there has been a steady rise in interest in studying novel cellular extensions and their potential roles in facilitating human diseases, including neurologic diseases, viral infectious diseases, cancer, and others. One of the exciting new aspects of this field is improved characterization and understanding of the functions and potential mechanisms of tunneling nanotubes (TNTs), which are actin-based filamentous protrusions that are structurally distinct from filopodia. TNTs form and connect cells at long distance and serve as direct conduits for intercellular communication in a wide range of cell types in vitro and in vivo.

A clinically applicable connectivity signature for glioblastoma includes the tumor network driver CHI3L1.

Tumor microtubes (TMs) connect glioma cells to a network with considerable relevance for tumor progression and therapy resistance. However, the determination of TM-interconnectivity in individual tumors is challenging and the impact on patient survival unresolved. Here, we establish a connectivity signature from single-cell RNA-sequenced (scRNA-Seq) xenografted primary glioblastoma (GB) cells using a dye uptake methodology, and validate it with recording of cellular calcium epochs and clinical correlations.

Cerebrospinal Fluid cfDNA Sequencing for Classification of Central Nervous System Glioma.

Purpose: Primary central nervous system (CNS) gliomas can be classified by characteristic genetic alterations. In addition to solid tissue obtained via surgery or biopsy, cell-free DNA (cfDNA) from cerebrospinal fluid (CSF) is an alternative source of material for genomic analyses.

Experimental Design: We performed targeted next-generation sequencing of CSF cfDNA in a representative cohort of 85 patients presenting at two neurooncological centers with suspicion of primary or recurrent glioma.

PerSurge (NOA-30) phase II trial of perampanel treatment around surgery in patients with progressive glioblastoma.

Background: Glioblastoma is the most frequent and a particularly malignant primary brain tumor with no efficacy-proven standard therapy for recurrence. It has recently been discovered that excitatory synapses of the AMPA-receptor subtype form between non-malignant brain neurons and tumor cells. This neuron-tumor network connectivity contributed to glioma progression and could be efficiently targeted with the EMA/FDA approved antiepileptic AMPA receptor inhibitor perampanel in preclinical studies.

A holistic view of the malignant organism we call glioblastoma.

Tumors are not simply a chaotic mass of mutated cells but can follow complex organizational principles, including in space. In this issue of Cell, Mathur and colleagues reconstruct a 3D genomic, epigenomic, and transcriptomic spatial cartograph of glioblastoma, offering a "whole-tumor" perspective with patterns of clonal expansion that are embedded in neurodevelopmental hierarchy.

[Glioblastomas exploit neuronal properties: a key to new forms of treatment?].

Recent research indicates that glioblastomas exhibit different neural properties that successfully promote tumor growth, colonize the brain and resist standard treatment. This opens up opportunities for new therapeutic strategies giving rise to the new research field of cancer neuroscience at the interface between oncology and neuroscience. It has been observed that glioblastomas as well as other incurable brain tumor entities, form multicellular tumor networks through long cell projections called tumor microtubes that are molecularly controlled by neuronal developmental mechanisms.

Neuroscience and oncology: state-of-the-art and new perspectives.

Purpose Of Review: Emerging discoveries suggest that both the central (CNS) and peripheral (PNS) nervous system are an important driver of cancer initiation, promotion, dissemination, and therapy resistance, not only in the brain but also in multiple cancer types throughout the body. This article highlights the most recent developments in this emerging field of research over the last year and provides a roadmap for the future, emphasizing its translational potential.

Recent Findings: Excitatory synapses between neurons and cancer cells that drive growth and invasion have been detected and characterized.

Inhibition of ATR opposes glioblastoma invasion through disruption of cytoskeletal networks and integrin internalization via macropinocytosis.

Background: Glioblastomas have highly infiltrative growth patterns that contribute to recurrence and poor survival. Despite infiltration being a critical therapeutic target, no clinically useful therapies exist that counter glioblastoma invasion. Here, we report that inhibition of ataxia telangiectasia and Rad 3 related kinase (ATR) reduces invasion of glioblastoma cells through dysregulation of cytoskeletal networks and subsequent integrin trafficking.

A H3K27M-targeted vaccine in adults with diffuse midline glioma.

Substitution of lysine 27 to methionine in histone H3 (H3K27M) defines an aggressive subtype of diffuse glioma. Previous studies have shown that a H3K27M-specific long peptide vaccine (H3K27M-vac) induces mutation-specific immune responses that control H3K27M tumors in major histocompatibility complex-humanized mice. Here we describe a first-in-human treatment with H3K27M-vac of eight adult patients with progressive H3K27M diffuse midline glioma on a compassionate use basis.

Glioblastoma revisited: from neuronal-like invasion to pacemaking.

In recent years, two developments have helped us to better understand the fundamental biology of glioblastoma: the description of a striking intratumoral heterogeneity including gene expression-based cell states, and the discovery that neuro-cancer interactions and cancer-intrinsic neurodevelopmental mechanisms are fundamental features of glioblastoma. In this opinion article, we aim to integrate both developments. We explain how two key disease features are characterized by different neural mechanisms related to distinct but plastic cancer cell states: first, the single cell-dominated invasive parts and second, the more solid parts which are dominated by communicating cell networks constantly activated by pacemaker-like glioblastoma cells.

The winner takes it all: Competition drives clonal selection in gliomagenesis.

The exact mechanisms that govern clonal dynamics and selection during early tumorigenesis remain largely elusive. Ceresa et al. provide experimental and mathematical evidence that MYC-dependent competition between individual clones is one driving force of brain tumor evolution, adding a winner/loser aspect to the picture that complements existing concepts.

A Cellular Ground Truth to Develop MRI Signatures in Glioma Models by Correlative Light Sheet Microscopy and Atlas-Based Coregistration.

Glioblastoma is the most common malignant primary brain tumor with poor overall survival. Magnetic resonance imaging (MRI) is the main imaging modality for glioblastoma but has inherent shortcomings. The molecular and cellular basis of MR signals is incompletely understood.

Individual glioblastoma cells harbor both proliferative and invasive capabilities during tumor progression.

Background: Glioblastomas are characterized by aggressive and infiltrative growth, and by striking heterogeneity. The aim of this study was to investigate whether tumor cell proliferation and invasion are interrelated, or rather distinct features of different cell populations.

Methods: Tumor cell invasion and proliferation were longitudinally determined in real-time using 3D in vivo 2-photon laser scanning microscopy over weeks.

Active Remodeling of Capillary Endothelium via Cancer Cell-Derived MMP9 Promotes Metastatic Brain Colonization.

Unlabelled: Crossing the blood-brain barrier is a crucial, rate-limiting step of brain metastasis. Understanding of the mechanisms of cancer cell extravasation from brain microcapillaries is limited as the underlying cellular and molecular processes cannot be adequately investigated using in vitro models and endpoint in vivo experiments. Using ultrastructural and functional imaging, we demonstrate that dynamic changes of activated brain microcapillaries promote the mandatory first steps of brain colonization.