title: A malignant cellular network in gliomas: potential clinical implications.
abstract: The recent discovery of distinct, ultra-long, and highly functional membrane protrusions in gliomas, particularly in astrocytomas, extends our understanding of how these tumors progress in the brain and how they resist therapies. In this article, we will focus on ideas on how to target these membrane protrusions, for which we have suggested the term "tumor microtubes" (TMs), and the malignant multicellular network they form. First, we discuss TM-specific features and their differential biological functions known so far. Second, the connection between 1p/19q codeletion and the inability to form functional TMs via certain neurodevelopmental pathways is presented; this could provide an explanation for the distinct clinical features of oligodendrogliomas. Third, the role of TMs for primary and potentially also adaptive resistance to cytotoxic therapies is highlighted. Fourth, avenues for therapeutic approaches to inhibit TM formation and/or function are discussed, with a focus on disruption (or exploitation) of network functionality. Finally, we propose ideas on how to use TMs as a biomarker in glioma patients. An increasing understanding of TMs in clinical and preclinical settings will show us whether they really are a long-sought-after Achilles' heel of treatment-resistant gliomas.
authors.affiliation: Neurology Clinic and National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany (M.O., G.S., W.W., F.W.); Clinical Cooperation Unit Neuro-oncology, German Cancer Consortium, German Cancer Research Center, Heidelberg, Germany (M.O., G.S., W.W., F.W.).
authors.forename: Matthias
authors.initials: M
authors.lastname: Osswald
authors.affiliation: Neurology Clinic and National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany (M.O., G.S., W.W., F.W.); Clinical Cooperation Unit Neuro-oncology, German Cancer Consortium, German Cancer Research Center, Heidelberg, Germany (M.O., G.S., W.W., F.W.).
authors.forename: Gergely
authors.initials: G
authors.lastname: Solecki
authors.affiliation: Neurology Clinic and National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany (M.O., G.S., W.W., F.W.); Clinical Cooperation Unit Neuro-oncology, German Cancer Consortium, German Cancer Research Center, Heidelberg, Germany (M.O., G.S., W.W., F.W.).
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wick
authors.affiliation: Neurology Clinic and National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany (M.O., G.S., W.W., F.W.); Clinical Cooperation Unit Neuro-oncology, German Cancer Consortium, German Cancer Research Center, Heidelberg, Germany (M.O., G.S., W.W., F.W.).
authors.forename: Frank
authors.initials: F
authors.lastname: Winkler
mesh_terms: D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology*; D002468:Cell Physiological Phenomena; D005910:Glioma / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D009434:Neural Pathways; D015398:Signal Transduction
keywords: 1p/19q codeletion; astrocytoma; glioblastoma; oligodendroglioma; resistance; tumor microtubes