Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 20, Issue 11, Pages -Publisher
MDPI
DOI: 10.3390/ijms20112746
Keywords
epithelial-mesenchymal transition (EMT); glioma; tumor heterogeneity; phenotypic plasticity; chemoresistance; proneural-mesenchymal transition (PMT); glioblastoma
Funding
- Associazione Italiana Ricerca sul Cancro (AIRC) [IG 18753, IG 18385]
- Regione Friuli Venezia Giulia (TNBCneo)
- Regione Friuli Venezia Giulia (RiFT)
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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.
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