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Proneural-Mesenchymal Transition: Phenotypic Plasticity to Acquire Multitherapy Resistance in Glioblastoma

1
National Research Council (CNR), Institute of Experimental Endocrinology and Oncology “G. Salvatore” (IEOS), 80131 Naples, Italy
2
Department of Life Sciences, University of Trieste, 34127 Trieste, Italy
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(11), 2746; https://doi.org/10.3390/ijms20112746
Received: 3 May 2019 / Revised: 31 May 2019 / Accepted: 2 June 2019 / Published: 4 June 2019
(This article belongs to the Special Issue Epithelial-Mesenchymal Transition (EMT))
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Abstract

Glioblastoma (GBM) is an extremely aggressive tumor of the central nervous system, with a prognosis of 12–15 months and just 3–5% of survival over 5 years. This is mainly because most patients suffer recurrence after treatment that currently consists in maximal resection followed by radio- and chemotherapy with temozolomide. The recurrent tumor shows a more aggressive behavior due to a phenotypic shift toward the mesenchymal subtype. Proneural-mesenchymal transition (PMT) may represent for GBM the equivalent of epithelial–mesenchymal transition associated with other aggressive cancers. In this review we frame this process in the high degree of phenotypic inter- and intra-tumor heterogeneity of GBM, which exists in different subtypes, each one characterized by further phenotypic variability in its stem-cell compartment. Under the selective pressure of different treatment agents PMT is induced. The mechanisms involved, as well as the significance of such event in the acquisition of a multitherapy resistance phenotype, are taken in consideration for future perspectives in new anti-GBM therapeutic options. View Full-Text
Keywords: epithelial–mesenchymal transition (EMT); glioma; tumor heterogeneity; phenotypic plasticity; chemoresistance; proneural-mesenchymal transition (PMT); glioblastoma epithelial–mesenchymal transition (EMT); glioma; tumor heterogeneity; phenotypic plasticity; chemoresistance; proneural-mesenchymal transition (PMT); glioblastoma
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Fedele, M.; Cerchia, L.; Pegoraro, S.; Sgarra, R.; Manfioletti, G. Proneural-Mesenchymal Transition: Phenotypic Plasticity to Acquire Multitherapy Resistance in Glioblastoma. Int. J. Mol. Sci. 2019, 20, 2746.

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