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Chemoresistance and Chemotherapy Targeting Stem-Like Cells in Malignant Glioma

  • Chapter
Stem Cell Biology in Neoplasms of the Central Nervous System

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 853))

Abstract

Glioblastoma remains a tumor with a dismal prognosis because of failure of current treatment. Glioblastoma cells with stem cell (GSC) properties survive chemotherapy and give rise to tumor recurrences that invariably result in the death of the patients. Here we summarize the current knowledge on chemoresistance of malignant glioma with a strong focus on GSC. Chemoresistant GSC are the most likely cause of tumor recurrence, but it remains controversial if GSC and under which conditions GSC are more chemoresistant than non-GSC within the tumor. Regardless of this uncertainty, the chemoresistance varies and it is mainly mediated by intrinsic factors. O6-methyl-guanidine methyltransferase (MGMT) remains the most potent mediator of chemoresistance, but disturbed mismatch repair system and multidrug resistance proteins contribute substantially. However, the intrinsic resistance by MGMT expression is regulated by extrinsic factors like hypoxia increasing MGMT expression and thereby resistance to alkylating chemotherapy. The search of new biomarkers helping to predict the tumor response to chemotherapy is ongoing and will complement the already known markers like MGMT.

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Authors and Affiliations

  1. Department of Pathology, Odense University Hospital, Odense C, Denmark

    Mia Dahl Sørensen, Sigurd Fosmark, Sofie Hellwege & Bjarne Winther Kristensen

  2. Institute of Clinical Research, University of Southern Denmark, Odense M, Denmark

    Mia Dahl Sørensen, Sigurd Fosmark, Sofie Hellwege, Dagmar Beier, Bjarne Winther Kristensen & Christoph Patrick Beier M.D.

  3. Department of Neurology, University of Southern Denmark, Sdr. Boulevard 19, 5000, Odense C, Denmark

    Dagmar Beier & Christoph Patrick Beier M.D.

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  1. Mia Dahl Sørensen
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    Moneeb Ehtesham

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Sørensen, M.D., Fosmark, S., Hellwege, S., Beier, D., Kristensen, B.W., Beier, C.P. (2015). Chemoresistance and Chemotherapy Targeting Stem-Like Cells in Malignant Glioma. In: Ehtesham, M. (eds) Stem Cell Biology in Neoplasms of the Central Nervous System. Advances in Experimental Medicine and Biology, vol 853. Springer, Cham. https://doi.org/10.1007/978-3-319-16537-0_7

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