Friday, November 15 2019

Glioblastomas are high-grade brain tumors characterized by very poor prognosis often with a survival below two years. Their aetiology and their pathogenesis is still unclear. Glioblastoma (GBM) is the most common type of brain tumor in adults; it represents 53.8% of all gliomas, and between all human tumors is one of those with higher mortality. Despite aggressive treatment at diagnosis, consisting in the surgical followed by radiation with concurrent and subsequent adjuvant chemotherapy with temozolomide, the cancer constantly recurs or progresses, with a median patient survival of 14.6 months representing the most aggressive and deadly cancer of all human cancers.

In glioblastoma progression it is difficult to stick to the classical cancer time line because this kind of tumor doesn’t go through gradual phases of progression, being aggressive right at the start. We have therefore identified several projects trying to respect the aims of our scientific strategic framework.

Prevention and early diagnosis

Project “Multiregion sequencing of glioblastoma samples to reconstruct phylogenetic branched evolution of tumor growth”.
FPS people involved: Sara Franceschi, Prospero Civita, Francesca Lessi, Michele Menicagli, Chiara M Mazzanti, Paolo Aretini.
External collaborators: Francesco Pasqualetti (U.O. Radiologia AOUP), Valerio Ortenzi (U.O. Anatomia Patologica AOUP), Cristian Scatena (U.O. Anatomia patologica AOUP), Giuseppe A Naccarato (U.O. Anatomia Patologica AOUP).

Better diagnosis and prognosis

Project “Spatial whole transcriptome analysis of tumor microenvironment in patients with primary glioblastoma”.
FPS people involved: Prospero Civita, Sara Franceschi, Chiara M Mazzanti, Francesca Lessi, Michele Menicagli.
External collaborators: Francesco Pasqualetti (U.O. Radiologia AOUP), Valerio Ortenzi (U.O. Anatomia Patologica AOUP), Cristian Scatena (U.O. Anatomia Patologica AOUP), Giuseppe A Naccarato (U.O. Anatomia Patologica AOUP).

New therapies

FPS Grant “Optical metabolic imaging (OMI) of glioblastoma patient derived organoids to assess treatment response and disease progression”
PI: Chiara Maria Mazzanti
Glioblastoma is a devastating disease that despite all the molecular information gathered so far, its optimal management remains elusive. Clinically and in preclinical drug development, there is a need for high-resolution, noninvasive, functional imaging tools to monitor and predict drug efficacy vs. lack of efficacy. Cellular metabolism is particularly sensitive to upstream molecular interventions, and therefore, may be a powerful biomarker of early drug response. Here we perform optical metabolic imaging of 3D organoids derived from primary human glioblastoma tumors to assess therapeutic response and disease progression.
People involved:
FPS: Sara Franceschi, Serena Barachini, Giovanni Signore, Francesca Lessi
Universita’ di Pisa/NEST: Ranieri Bizzarri
Azienda Ospedaliera Pisa and Livorno: Francesco Pasqualetti, Fabio Di Martino, Riccardo Vannozzi, Orazio Santonocito, Antonio Giuseppe Naccarato
External collaborators :  Paul Mulholland, Diego Ottaviani (University College of London, UK), Geoff Pilkington, Prospero Civita (University of Portsmouth,UK)

Project “Mitochondrial enzyme GLUD2 plays a role in glioblastoma progression”.
FPS people involved: Sara Franceschi, Chiara M Mazzanti, Francesca Lessi, Michele Menicagli, Liam McDonnell, Marialaura Dilillo, Davide Pellegrini.
External collaborators: Francesco Pasqualetti (U.O. Radiologia AOUP), Valerio Ortenzi (U.O. Anatomia Patologica AOUP) , Cristian Scatena (U.O. Anatomia Patologica AOUP), Giuseppe A Naccarato (U.O. Anatomia Patologica AOUP), Michela Ori (Universita’ di Pisa).

Project “A Rho GTPase-activating protein reduces tumor growth and spares neuron structure and function”.
FPS people involved: Liam McDonnell
External collaborators: E Vannini, F Olimpico, S Middei, M Ammassari-Teule, EL de Graaf, G Schmidt, A Fabbri, C Fiorentini, L Baroncelli, M Costa, M Caleo.