Glioblastoma

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Our focus

Our initial focus is on glioblastoma (grade IV astrocytoma), a particularly lethal form of brain cancer that is characterized by diffusely infiltrative growth. Glioblastoma is a major unmet medical need globally.

Our collaborators

Our collaborators at the University of Heidelberg and German Cancer Research Center (DKFZ) have convincingly shown that the tumour cells in glioblastoma interconnect through structures called tumour microtubes to form a functional network that enables brain invasion, proliferation, and resistance to chemo- and radiotherapy.

There is also strong human genetic validation for the role of tumour microtubes in glioblastoma (astrocytoma); less aggressive oligodendroglial brain tumours have a genetic co-deletion (1p19q) and are unable to form intercellular networks through tumour microtubes, are chemo- and radiosensitive and have a better prognosis. Experiments have identified genes that are lost in the 1p19q co-deletion and shown that it is possible to render an astrocytoma phenotype into a oligodendroglioma phenotype by knocking down certain genetic targets, and vice versa.

Please find, below, links to some key publications from our collaborators.

REFERENCES

Osswald M, Jung E, Sahm F, et al. Brain tumour cells interconnect to a functional and resistant network. Nature. 2015; 528(7580):93-98.
Winkler F, Wick W. Harmful networks in the brain and beyond. Science. 2018; 359(6380):1100-1101.
Osswald M, Solecki G, Wick W, Winkler F. A malignant cellular network in gliomas: potential clinical implications. Neuro Oncol. 2016; 18(4):479-485.
Jung E, Osswald M, Blaes J, et al. Tweety-Homolog 1 Drives Brain Colonization of Gliomas. J Neurosci. 2017; 37(29):6837-6850.
Weil S, Osswald M, Solecki G, et al. Tumor microtubes convey resistance to surgical lesions and chemotherapy in gliomas. Neuro Oncol. 2017.
Baker M. How the Internet of cells has biologists buzzing. Nature. 2017; 549(7672):322-324.

Portela M, Venkataramani V, Fahey-Lozano N, et al. WNT vampirization by glioblastoma leads to tumor growth and neurodegeneration. bioRxiv. 2018:428953.
Linkous A, Balamatsias D, Snuderl M, et al. Modeling Patient-Derived Glioblastoma with Cerebral Organoids. Cell Rep. 2019; 26(12):3203-3211 e3205.
da Silva B, Polson ES, Droop A, et al. Chemically-induced Neurite-like Outgrowth Reveals Multicellular Network Function in Patient-derived Glioblastoma Cells. bioRxiv. 2018:467654.
Osswald M, Jung E, Wick W, Winkler F. Tunneling nanotube-like structures in brain tumors. CANCER REPORTS. 0(0):e1181.
Weller M, Wick W, Aldape K, et al. Glioma. Nature Reviews Disease Primers. 2015; 1:15017.