CNS cancer articles within Nature

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  • Article
    | Open Access

    In glioma, malignant synapses hijack mechanisms of synaptic plasticity to increase glutamate-dependent currents in tumour cells and the formation of neuron–glioma synapses, thereby promoting tumour proliferation and progression.

    • Kathryn R. Taylor
    • , Tara Barron
    •  & Michelle Monje

  • Article
    | Open Access

    Sturgeon is a pretrained neural network that uses incremental results from nanopore sequencing to rapidly classify central nervous system tumours and can be used to aid critical decision-making during surgery.

    • C. Vermeulen
    • , M. Pagès-Gallego
    •  & J. de Ridder

  • Article |

    Callosal projection neurons located in the hemisphere contralateral to primary glioblastoma promote progression and widespread infiltration, and screening of axon guidance genes identified SEMA4F as a key regulator of tumourigenesis and activity-dependent progression.

    • Emmet Huang-Hobbs
    • , Yi-Ting Cheng
    •  & Benjamin Deneen

  • Article |

    Glioblastoma stem cells co-opt lysine uptake and degradation to shunt the production of crotonyl-CoA, remodelling the chromatin landscape to evade interferon-induced intrinsic effects on glioblastoma stem cell maintenance and extrinsic effects on immune response.

    • Huairui Yuan
    • , Xujia Wu
    •  & Jeremy N. Rich

  • Article
    | Open Access

    Imaging mass cytometry of human brain tumours provides spatial information that, combined with existing transcriptomic data, reveals the existence of a cellular neighbourhood containing a rare macrophage population associated with prolonged survival.

    • Elham Karimi
    • , Miranda W. Yu
    •  & Logan A. Walsh

  • Article |

    Integrated single-cell atlases of human fetal cerebella and MBs show potential cell populations predisposed to transformation and regulatory circuitries underlying tumour cell states and oncogenesis, highlighting hitherto unrecognized transitional progenitor intermediates predictive of disease prognosis.

    • Zaili Luo
    • , Mingyang Xia
    •  & Q. Richard Lu

  • Article |

    Multi-omic mapping shows that group 3 and group 4 medulloblastomas have a common, human-specific developmental origin in the cerebellar rhombic lip, providing a basis for their ambiguous molecular features and overlapping anatomical location, and for the difficulty of modelling these tumours in mice.

    • Kyle S. Smith
    • , Laure Bihannic
    •  & Paul A. Northcott

  • Article
    | Open Access

    The combination of the brain-permeable mTOR inhibitor RapaLink-1 and the brain-impermeable FKBP12 ligand RapaBlock enable brain-specific inhibition of mTOR.

    • Ziyang Zhang
    • , Qiwen Fan
    •  & Kevan M. Shokat

  • Article
    | Open Access

    A phase I dose-escalation trial of GD2-CAR T cells in children and young adults with diffuse midline gliomas to assess the feasibility of manufacturing, safety and tolerability, and to preliminarily assess efficacy.

    • Robbie G. Majzner
    • , Sneha Ramakrishna
    •  & Michelle Monje

  • Article
    | Open Access

    A phase 1 clinical trial provides evidence that a vaccine against mutant IDH1 is safe and produces a T helper immune response in patients with glioma.

    • Michael Platten
    • , Lukas Bunse
    •  & Wolfgang Wick

  • Article |

    Analyses of primary and relapse samples of embryonal tumours with multilayered rosettes provide insights into the molecular mechanisms that underlie the development and opportunities for the treatment of this deadly disease.

    • Sander Lambo
    • , Susanne N. Gröbner
    •  & Marcel Kool

  • Article |

    The GLASS Consortium studies the evolutionary trajectories of 222 patients with a diffuse glioma to aid in our understanding of tumour progression and treatment failure

    • Floris P. Barthel
    • , Kevin C. Johnson
    •  & Roel G. W. Verhaak

  • Article |

    Sequencing data from the developing cerebellum are compared with bulk sequencing data from paediatric tumours, providing insights into their potential origins and suggesting that many cerebellar tumours have their origins early in utero.

    • Maria C. Vladoiu
    • , Ibrahim El-Hamamy
    •  & Michael D. Taylor

  • Letter |

    In a phase I trial, highly individualized peptide vaccines against unmutated tumour antigens and neoepitopes elicited sustained responses in CD8+ and CD4+ T cells, respectively, in patients with newly diagnosed glioblastoma.

    • Norbert Hilf
    • , Sabrina Kuttruff-Coqui
    •  & Wolfgang Wick

  • Letter |

    Neoantigen-targeting vaccines are a feasible therapy for tumours with a low mutation burden and immunologically ‘cold’ tumour microenvironment, as neoantigen-specific T cells from the peripheral blood migrate into intracranial glioblastoma, thereby altering the immune milieu of the glioblastoma.

    • Derin B. Keskin
    • , Annabelle J. Anandappa
    •  & David A. Reardon

  • Letter |

    The growth of adult and paediatric brain tumours depends on a microenvironmental signalling pathway involving the activity-regulated secretion of neuroligin-3 (NLGN3) from normal neurons and oligodendrocyte precursor cells, highlighting the potential of NLGN3 as a therapeutic target.

    • Humsa S. Venkatesh
    • , Lydia T. Tam
    •  & Michelle Monje

  • Article
    | Open Access

    Genomic analysis of 491 medulloblastoma samples, including methylation profiling of 1,256 cases, effectively assigns candidate drivers to most tumours across all molecular subgroups.

    • Paul A. Northcott
    • , Ivo Buchhalter
    •  & Peter Lichter

  • Letter |

    An in vivo RNA interference screening strategy in glioblastoma enabled the identification of a host of epigenetic targets required for glioblastoma cell survival that were not identified by parallel standard screening in cell culture, including the transcription pause–release factor JMJD6, and could be a powerful tool to uncover new therapeutic targets in cancer.

    • Tyler E. Miller
    • , Brian B. Liau
    •  & Jeremy N. Rich

  • Article |

    Genomic studies of the paediatric brain tumour medulloblastoma have revealed four clinically distinct molecular subgroups; here active gene regulatory elements in 28 primary medulloblastoma tissues are mapped to reveal differentially regulated enhancers across the different subgroups, allowing insights into the transcription factors that characterize subgroup divergence and the cellular origin of the poorly characterized Group 3 and 4 subgroups.

    • Charles Y. Lin
    • , Serap Erkek
    •  & Paul A. Northcott

  • Article |

    To address the question of whether a recurrent tumour is genetically similar to the tumour at diagnosis, the evolution of medulloblastoma has been studied in both an in vivo mouse model of clinical tumour therapy as well as in humans with recurrent disease; targeted tumour therapies are usually based on targets present in the tumour at diagnosis but the results from this study indicate that post-treatment recurring tumours (compared with the tumour at diagnosis) have undergone substantial clonal divergence of the initial dominant tumour clone.

    • A. Sorana Morrissy
    • , Livia Garzia
    •  & Michael D. Taylor

  • Article |

    HIFα transcription factors are highly expressed in cancer stem cells from glioma; DYRK1 kinases inhibit the protein ID2 to modulate the level of HIF2α and the tumorigenic properties of glioblastoma-associated cancer stem cells.

    • Sang Bae Lee
    • , Veronique Frattini
    •  & Anna Lasorella

  • Letter |

    An epigenetic mechanism in which gain-of-function IDH mutations promote gliomagenesis by disrupting chromosomal topology is presented, with IDH mutations causing the binding sites of the methylation-sensitive insulator CTCF to become hypermethylated; disruption of a CTCF boundary near the glioma oncogene PDGFRA allows a constitutive enhancer to contact and activate the oncogene aberrantly.

    • William A. Flavahan
    • , Yotam Drier
    •  & Bradley E. Bernstein

  • Article |

    Brain tumours are difficult to treat because of their propensity to infiltrate brain tissue; here long processes, or tumour microtubes, extended by astrocytomas are shown to promote brain infiltration and to create an interconnected network that enables multicellular communication and that protects the tumours from radiotherapy-induced cell death, suggesting that disruption of the network could be a new therapeutic approach.

    • Matthias Osswald
    • , Erik Jung
    •  & Frank Winkler

  • Letter |

    A clinical trial in patients with glioblastoma shows increased immune and anti-tumour responses to dendritic cell vaccination after pre-conditioning the site of vaccination with tetanus toxoid (Td); similar results are also seen in mice in part due to the actions of the chemokine CCL3, and the findings may represent new ways to improve the efficacy of anti-cancer vaccines.

    • Duane A. Mitchell
    • , Kristen A. Batich
    •  & John H. Sampson

  • Letter |

    The mutant IDH1 protein, which is expressed in a large fraction of human gliomas, is shown to be immunogenic; mutant-specific immune responses can be detected in patients with IDH1 mutated gliomas and generated in mice and are shown to treat established IDH1 mutant tumours in a syngeneic MHC humanized mouse model in a CD4 T-cell-dependent manner.

    • Theresa Schumacher
    • , Lukas Bunse
    •  & Michael Platten

  • Letter |

    Intracranial germ cell tumours are rare tumours affecting mainly male adolescents, mainly in Asia; here the authors identify frequent mutations in the KIT/RAS and AKT/mTOR signalling pathways as well as rare germline variants in JMJD1C, suggesting potential therapeutic strategies focusing on the inhibition of KIT/RAS activation and the AKT1/mTOR pathway.

    • Linghua Wang
    • , Shigeru Yamaguchi
    •  & Ching C. Lau

  • Letter |

    Medulloblastoma is a malignant childhood brain tumour presenting major clinical challenges; here, a comprehensive genome-wide DNA methylation data set from human and mouse tumours, coupled with analysis of histone modifications, RNA transcripts and genome sequencing, uncovers a wealth of alterations that provide insights into the epigenetic regulation of transcription and genome organization in medulloblastoma pathogenesis.

    • Volker Hovestadt
    • , David T. W. Jones
    •  & Peter Lichter

  • Article |

    At least two-thirds of supratentorial ependymomas contain oncogenic fusions between RELA, the principal effector of nuclear factor-κB (NF-κB) signalling, and uncharacterized gene C11orf95; C11orf95–RELA fusion proteins translocate spontaneously to the nucleus to activate NF-κB target genes, and rapidly transform neural stem cells to form tumours in mice

    • Matthew Parker
    • , Kumarasamypet M. Mohankumar
    •  & Richard J. Gilbertson

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