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Digital archive of theses discussed at the University of Pisa

 

Thesis etd-05122021-113254


Thesis type
Tesi di dottorato di ricerca
Author
PIETROBONO, DEBORAH
URN
etd-05122021-113254
Thesis title
Signalling pathways in Glioblastoma as target for innovative therapy
Academic discipline
BIO/10
Course of study
SCIENZA DEL FARMACO E DELLE SOSTANZE BIOATTIVE
Supervisors
tutor Prof.ssa Trincavelli, Maria Letizia
relatore Dott.ssa Giacomelli, Chiara
Keywords
  • Adenosine
  • Bax
  • Cancer stem cells
  • Glioblastoma
  • Mesenchymal Stem Cells
  • p53
  • Tumor microenvironment
Graduation session start date
19/05/2021
Availability
Withheld
Release date
19/05/2091
Summary
Glioblastoma (GBM) is an aggressive and invasive brain tumor. The first line treatment usually is the surgical resection, followed by radiotherapy and the administration of the alkylating agent Temozolomide. Significant intra- and inter-tumor heterogeneity have been associated with aberrations in different intracellular pathways and a peculiar tumor microenvironment (TME) that contributes to GBM aggressiveness. In GBM, tumor cells can escape from apoptosis because there is an overexpression of anti-apoptotic proteins and an inhibition of pro-apoptotic ones, like Bax. The tumor progression could be due also to the deregulation of the oncosuppressor protein p53. The overexpression of p53 inhibitor, MDM2, often occurs in GBM promoting its proliferation. The reactivation of p53 endogenous function can represent an important target in the development of effective GBM treatment. The failure of GBM treatment is also due to the presence of a peculiar TME. Tumor cells regulate the function of cellular and non-cellular components through complex signalling pathways and could use the non-malignant cells to work for their benefit. Adenosine is one of the main immunomodulatory mediators involved in tumor development. Herein, we deeply investigated the aberrant intracellular signalling pathways involved in GBM pathogenesis and how the modulation of these pathways could prevent GBM aggressiveness.
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