The role of hypoxia and SRC tyrosine kinase in glioblastoma invasiveness and radioresistance

Filippo Torrisi (1) , Nunzio Vicario (1) , Federica Spitale (1) , Francesco Cammarata (2) , Luigi Minafra (2) , Lucia Salvatorelli (1) , Giorgio Russo (2) , Giacomo Cuttone (3) , Samuel Valable (4) , Rosario Gulino (1) , Gaetano Magro (1) , Rosalba Parenti (1)

1 Unict - Università degli studi di Catania = University of Catania
2 LNS - Laboratori Nazionali del Sud
3 INFN - Istituto Nazionale di Fisica Nucleare, Sezione di Catania
4 ISTCT - Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales

Advances in functional imaging are supporting neurosurgery and radiotherapy for glioblastoma, which still remains the most aggressive brain tumor with poor prognosis. The typical infiltration pattern of glioblastoma, which impedes a complete surgical resection, is coupled with a high rate of invasiveness and radioresistance, thus further limiting efficient therapy, leading to inevitable and fatal recurrences. Hypoxia is of crucial importance in gliomagenesis and, besides reducing radiotherapy efficacy, also induces cellular and molecular mediators that foster proliferation and invasion. In this review, we aimed at analyzing the biological mechanism of glioblastoma invasiveness and radioresistance in hypoxic niches of glioblastoma. We also discussed the link between hypoxia and radiation-induced radioresistance with activation of SRC proto-oncogene non-receptor tyrosine kinase, prospecting potential strategies to overcome the current limitation in glioblastoma treatment.

Mots clés: Glioblastoma; hypoxia; radioresistance; invasion; SRC tyrosine kinase; targeted therapy

Domaines: Cancer; Neurobiologie

Filippo Torrisi, Nunzio Vicario, Federica Spitale, Francesco Cammarata, Luigi Minafra, et al.. The role of hypoxia and SRC tyrosine kinase in glioblastoma invasiveness and radioresistance. Cancers, 2020, 12 (10), pp.2860. ⟨10.3390/cancers12102860⟩. ⟨hal-02989744⟩