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Published on: February 24, 2021
A malignant cellular network in gliomas: potential clinical implications
Matthias Osswald1, Gergely Solecki1, Wolfgang Wick1
1Neurology 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.).
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.
Insights
Glioma tumors form ultra-long "tumor microtubes" (TMs) that aid their brain progression and therapy resistance. Targeting these TMs offers a potential new strategy for treating aggressive brain cancers.
Area of Science:
- Neuro-oncology
- Cancer Biology
- Cellular Neuroscience
Background:
- Gliomas, particularly astrocytomas, exhibit unique, ultra-long membrane protrusions called tumor microtubes (TMs).
- These TMs form a malignant multicellular network, influencing tumor progression and therapeutic resistance.
Purpose of the Study:
- To explore targeting strategies for tumor microtubes (TMs) in gliomas.
- To discuss TM-specific features, biological functions, and their role in therapy resistance.
- To propose TMs as potential biomarkers for glioma patients.
Main Methods:
- Review of TM-specific features and biological functions.
- Analysis of the link between 1p/19q codeletion and TM formation.
- Discussion of therapeutic approaches targeting TM network functionality.
- Exploration of TMs as potential biomarkers.
Main Results:
- TMs are crucial for glioma progression and resistance to cytotoxic therapies.
- The inability to form functional TMs may explain distinct clinical features in oligodendrogliomas (linked to 1p/19q codeletion).
- Disrupting TM network functionality presents a promising therapeutic avenue.
Conclusions:
- Tumor microtubes (TMs) represent a significant factor in glioma aggressiveness and treatment failure.
- Targeting TMs offers a novel therapeutic strategy and potential biomarker for glioma management.
- Further understanding of TMs could reveal an Achilles' heel for treatment-resistant gliomas.
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