Glioblastoma: Pathogenesis and Current Status of Chemotherapy and Other Novel Treatments

Rajaratnam, Vilashini; Islam, Mohammad Mohiminul; Yang, Maixee; Slaby, Rachel; Ramirez, Hilda Martinez; Mirza, Shama P.

doi:10.3390/cancers12040937

Cited by 105 publications

(96 citation statements)

References 161 publications

(129 reference statements)

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“…GBM has a global incidence of 10 per 100,000 of the population and can affect people of all ages, although peak age of diagnosis falls between 45 and 75 years [ 6 ]. Primary GBM (those that arise de novo) account for 95% of tumours, whereas those arising from precursor less malignant gliomas (secondary, usually with an IDH mutation) account for the remaining 5% [ 7 ]. Treatment prospects are bleak for GBM; initial surgical intervention is the main predictor of outcome and is necessary to gain a clear histological diagnosis for the glioma.…”

Section: Gliomamentioning

confidence: 99%

Ion Channels as Therapeutic Targets in High Grade Gliomas

Griffin

Khan

Basu

et al. 2020

Cancers

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Glioblastoma multiforme (GBM) is a lethal brain cancer with an average survival of 14–15 months even with exhaustive treatment. High grade gliomas (HGG) represent the leading cause of CNS cancer-related death in children and adults due to the aggressive nature of the tumour and limited treatment options. The scarcity of treatment available for GBM has opened the field to new modalities such as electrotherapy. Previous studies have identified the clinical benefit of electrotherapy in combination with chemotherapeutics, however the mechanistic action is unclear. Increasing evidence indicates that not only are ion channels key in regulating electrical signaling and membrane potential of excitable cells, they perform a crucial role in the development and neoplastic progression of brain tumours. Unlike other tissue types, neural tissue is intrinsically electrically active and reliant on ion channels and their function. Ion channels are essential in cell cycle control, invasion and migration of cancer cells and therefore present as valuable therapeutic targets. This review aims to discuss the role that ion channels hold in gliomagenesis and whether we can target and exploit these channels to provide new therapeutic targets and whether ion channels hold the mechanistic key to the newfound success of electrotherapies.

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Section: Gliomamentioning

confidence: 99%

Ion Channels as Therapeutic Targets in High Grade Gliomas

Griffin

Khan

Basu

et al. 2020

Cancers

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“…This combination of treatment has demonstrated a 2-month increase in life expectancy from 12.2 to 14.6 months, and a 16% increase in 2-year survival (Stupp et al 2009). Over the past decade, many drugs have entered clinical trials for treatment of gliomas including epidermal growth factor receptor (EGFR) targeted therapies (Rajaratnam et al 2020), protein kinase B (Akt) inhibitors (Kaley et al 2019;Wen et al 2013), mutant isocitrate dehydrogenase (IDH1) inhibitors (Fan et al 2020) and calcium channel inhibitors (Holdhoff et al 2017). Despite intense research efforts, minimal changes to GBM patient life expectancy have been observed since the introduction of TMZ therapy over 10 years ago.…”

Section: Introductionmentioning

confidence: 99%

Arginine methylation: the promise of a ‘silver bullet’ for brain tumours?

et al. 2021

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Despite intense research efforts, our pharmaceutical repertoire against high-grade brain tumours has not been able to increase patient survival for a decade and life expectancy remains at less than 16 months after diagnosis, on average. Inhibitors of protein arginine methyltransferases (PRMTs) have been developed and investigated over the past 15 years and have now entered oncology clinical trials, including for brain tumours. This review collates recent advances in the understanding of the role of PRMTs and arginine methylation in brain tumours. We provide an up-to-date literature review on the mechanisms for PRMT regulation. These include endogenous modulators such as alternative splicing, miRNA, post-translational modifications and PRMT–protein interactions, and synthetic inhibitors. We discuss the relevance of PRMTs in brain tumours with a particular focus on PRMT1, -2, -5 and -8. Finally, we include a future perspective where we discuss possible routes for further research on arginine methylation and on the use of PRMT inhibitors in the context of brain tumours.

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“…G lioblastoma is the most common malignant primary brain tumor and is the focus of extensive basic and clinical research efforts targeting improved therapies. 1,2 Technologies related to the establishment of primary low passage tumor cultures are increasingly important to oncology research and practice. [3][4][5][6][7] However, processing of fresh tumor specimens for the establishment of primary cultures on the day of surgical collection is logistically difficult.…”

Section: Introductionmentioning

confidence: 99%

Optimization of Viable Glioblastoma Cryopreservation for Establishment of Primary Tumor Cell Cultures

Valyi‐Nagy

Betsou²,

Susma

et al. 2021

Biopreservation and Biobanking

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Background: Technologies related to the establishment of primary tumor cell cultures from solid tumors, including glioblastoma, are increasingly important to oncology research and practice. However, processing of fresh tumor specimens for establishment of primary cultures on the day of surgical collection is logistically difficult. The feasibility of viable cryopreservation of glioblastoma specimens, allowing for primary culture establishment weeks to months after surgical tumor collection and freezing, was demonstrated by Mullins et al. in 2013, with a success rate of 59% that was not significantly lower than that achieved with fresh tumor tissue. However, research targeting optimization of viable glioblastoma cryopreservation protocols for establishment of primary tumor cultures has been limited. Objectives: The objective of this study was to optimize glioblastoma cryopreservation methods for viable cryobanking and to determine if two-dimensional (2D) or three-dimensional (3D) culture conditions were more supportive of glioblastoma growth after thawing of frozen tumor specimens. Methods: Portions of eight human glioblastoma specimens were cryopreserved by four different protocols differing in the time of enzymatic digestion (before or after cryopreservation), and in the type of cryopreservation media (CryoStor CS10 or 10% dimethyl sulfoxide and 90% fetal calf serum). After 1 month, frozen tissues were thawed, enzymatically digested, if not digested before, and used for initiation of 2D or 3D primary tumor cultures to determine viability. Results: Among the tested cryopreservation and culturing protocols, the most efficient combinations of cryopreservation and culture were those associated with the use of CryoStor CS10 cryopreservation medium, enzymatic digestion before freezing, and 2D culturing after thawing with a successful culture rate of 8 out of 8 cases (100%). Two-dimensional cultures were in general more efficient for the support of tumor cell growth after thawing than 3D cultures. Conclusions: This study supports development of evidence-based viable glioblastoma cryopreservation methods for use in glioblastoma biobanking and research.

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Glioblastoma: Pathogenesis and Current Status of Chemotherapy and Other Novel Treatments

Cited by 105 publications

References 161 publications

Ion Channels as Therapeutic Targets in High Grade Gliomas

Ion Channels as Therapeutic Targets in High Grade Gliomas

Arginine methylation: the promise of a ‘silver bullet’ for brain tumours?

Optimization of Viable Glioblastoma Cryopreservation for Establishment of Primary Tumor Cell Cultures

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