Pathogenetic Features and Current Management of Glioblastoma

Abstract

Glioblastoma (GBM) is the most common form of primary malignant brain tumor with a devastatingly poor prognosis. The disease does not discriminate, affecting adults and children of both sexes, and has an average overall survival of 12–15 months, despite advances in diagnosis and rigorous treatment with chemotherapy, radiation therapy, and surgical resection. In addition, most survivors will eventually experience tumor recurrence that only imparts survival of a few months. GBM is highly heterogenous, invasive, vascularized, and almost always inaccessible for treatment. Based on all these outstanding obstacles, there have been tremendous efforts to develop alternative treatment options that allow for more efficient targeting of the tumor including small molecule drugs and immunotherapies. A number of other strategies in development include therapies based on nanoparticles, light, extracellular vesicles, and micro-RNA, and vessel co-option. Advances in these potential approaches shed a promising outlook on the future of GBM treatment. In this review, we briefly discuss the current understanding of adult GBM’s pathogenetic features that promote treatment resistance. We also outline novel and promising targeted agents currently under development for GBM patients during the last few years with their current clinical status.

The Multifaceted Role of Extracellular Vesicles in Glioblastoma: microRNA Nanocarriers for Disease Progression and Gene Therapy

“…A subsequent study done by Brennan et al [ 6 ] identified other significantly mutated genes in GB: IDH1, PDGFRA, leucine-zipper-like transcriptional regulator 1 (LZTR1), spectrin alpha 1 (SPTA1), ATRX, gamma-aminobutyric acid type A receptor subunit alpha 6 (GABRA6) and KEL, as well as amplifications in chromosome 4 (PDGFRA), chromosome 7 (EGFR, MET, CDK6) and chromosome 12 (CDK4, MDM2). Additionally, a TCGA-based study showed that GB tumors often exhibit alterations of the TP53, RB and RTK/Ras/PI3K signaling pathways [ 6 ], contributing to cancer cell migration, invasion, proliferation, differentiation and survival [ 105 ].…”

Glutamatergic Mechanisms in Glioblastoma and Tumor-Associated Epilepsy

“…The current oncological treatment of glioblastoma patients has been excellently reviewed elsewhere [ 129 ]. Although temozolomide might exert some anticonvulsant effects [ 130 ], here we will focus on pharmacological means of addressing glioma-associated seizures since there is an increasing understanding of the shared mechanisms of tumor progression and epileptogenicity, suggesting that certain compounds could establish novel strategies for the treatment of glioblastoma patients presenting epileptic seizures.…”

A Multi-Scale and Multi-Technique Approach for the Characterization of the Effects of Spatially Fractionated X-ray Radiation Therapies in a Preclinical Model

“…For a full dataset, it is sufficient to label the 10% of the available slices, the full-volume segmentation will be done by interpolation. After the tumor is correctly identified (6), binary images are produced (7) and the tumor volume can be quantified by the Analyze Particles Fiji plugin (8). This volume can also be rendered in 3D via the software VGStudio MAX 4.3 together with the original brain dataset (9).…”

“…It has a poor prognosis with a survival ranging from 7 months [ 3 ] to 12–15 months [ 4 , 5 ] with a long-term survival probability less than 3% [ 6 ]. GBM treatment involves surgery, chemotherapy, and radiation therapy (RT); due to the radio- and chemo-resistance and highly infiltrative growth of GBM, present treatments are only able to slow down the development of the disease permitting an increase of the survival by a few months [ 7 ]. For all these reasons, there is the need for an effective therapy for the management of gliomas.…”