The Alcatraz-Strategy: a roadmap to break the connectivity barrier in malignant brain tumours.

Autor: Schneider M; Department of Neurosurgery, University Hospital Bonn, Germany.; Brain Tumour Translational Research Group, University Hospital Bonn, Germany., Potthoff AL; Department of Neurosurgery, University Hospital Bonn, Germany.; Brain Tumour Translational Research Group, University Hospital Bonn, Germany., Karpel-Massler G; Department of Neurosurgery, University Medical Center Ulm, Germany., Schuss P; Department of Neurosurgery, BG Klinikum Unfallkrankenhaus Berlin gGmbH, Germany., Siegelin MD; Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA., Debatin KM; Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Germany., Duffau H; Department of Neurosurgery, Gui de Chauliac Hospital, Montpellier University Medical Center, France.; Team 'Plasticity of Central Nervous System, Stem Cells and Glial Tumors,' National Institute for Health and Medical Research (INSERM), U1191 Laboratory, Institute of Functional Genomics, University of Montpellier, France., Vatter H; Department of Neurosurgery, University Hospital Bonn, Germany.; Brain Tumour Translational Research Group, University Hospital Bonn, Germany., Herrlinger U; Brain Tumour Translational Research Group, University Hospital Bonn, Germany.; Division of Clinical Neuro-Oncology, Department of Neurology, University Hospital Bonn, Germany., Westhoff MA; Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Germany.
Jazyk: angličtina
Zdroj: Molecular oncology [Mol Oncol] 2024 Apr 03. Date of Electronic Publication: 2024 Apr 03.
DOI: 10.1002/1878-0261.13642
Abstrakt: In recent years, the discovery of functional and communicative cellular tumour networks has led to a new understanding of malignant primary brain tumours. In this review, the authors shed light on the diverse nature of cell-to-cell connections in brain tumours and propose an innovative treatment approach to address the detrimental connectivity of these networks. The proposed therapeutic outlook revolves around three main strategies: (a) supramarginal resection removing a substantial portion of the communicating tumour cell front far beyond the gadolinium-enhancing tumour mass, (b) morphological isolation at the single cell level disrupting structural cell-to-cell contacts facilitated by elongated cellular membrane protrusions known as tumour microtubes (TMs), and (c) functional isolation at the single cell level blocking TM-mediated intercellular cytosolic exchange and inhibiting neuronal excitatory input into the malignant network. We draw an analogy between the proposed therapeutic outlook and the Alcatraz Federal Penitentiary, where inmates faced an impassable sea barrier and experienced both spatial and functional isolation within individual cells. Based on current translational efforts and ongoing clinical trials, we propose the Alcatraz-Strategy as a promising framework to tackle the harmful effects of cellular brain tumour networks.
(© 2024 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)
Databáze: MEDLINE
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