Animal Models in Glioblastoma: Use in Biology and Developing Therapeutic Strategies

Schuhmacher, Alberto J.; Squatrito, Massimo

doi:10.1007/978-3-319-56820-1_9

Cited by 4 publications

(4 citation statements)

References 129 publications

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“…Some of the current and state-of-the-art strategies for developing animal models of GBM will be summarized here. [This subject has been reviewed extensively by Huszthy et al (2012) , Miyai et al (2017) , and Schuhmacher and Squatrito (2017) ].…”

Section: Emerging Targets In Glioblastomamentioning

confidence: 99%

Current Challenges and Opportunities in Treating Glioblastoma

et al. 2018

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Glioblastoma multiforme (GBM), the most common and aggressive primary brain tumor, has a high mortality rate despite extensive efforts to develop new treatments. GBM exhibits both intra- and intertumor heterogeneity, lending to resistance and eventual tumor recurrence. Large-scale genomic and proteomic analysis of GBM tumors has uncovered potential drug targets. Effective and “druggable” targets must be validated to embark on a robust medicinal chemistry campaign culminating in the discovery of clinical candidates. Here, we review recent developments in GBM drug discovery and delivery. To identify GBM drug targets, we performed extensive bioinformatics analysis using data from The Cancer Genome Atlas project. We discovered 20 genes, BOC, CLEC4GP1, ELOVL6, EREG, ESR2, FDCSP, FURIN, FUT8-AS1, GZMB, IRX3, LITAF, NDEL1, NKX3-1, PODNL1, PTPRN, QSOX1, SEMA4F, TH, VEGFC, and C20orf166AS1 that are overexpressed in a subpopulation of GBM patients and correlate with poor survival outcomes. Importantly, nine of these genes exhibit higher expression in GBM versus low-grade glioma and may be involved in disease progression. In this review, we discuss these proteins in the context of GBM disease progression. We also conducted computational multi-parameter optimization to assess the blood-brain barrier (BBB) permeability of small molecules in clinical trials for GBM treatment. Drug delivery in the context of GBM is particularly challenging because the BBB hinders small molecule transport. Therefore, we discuss novel drug delivery methods, including nanoparticles and prodrugs. Given the aggressive nature of GBM and the complexity of targeting the central nervous system, effective treatment options are a major unmet medical need. Identification and validation of biomarkers and drug targets associated with GBM disease progression present an exciting opportunity to improve treatment of this devastating disease.

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Section: Emerging Targets In Glioblastomamentioning

confidence: 99%

Current Challenges and Opportunities in Treating Glioblastoma

et al. 2018

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“…Several models by a variety of species have been developed to date, the common goal of all of which is to produce tumors that recapitulate human disease. It is obvious that none of the animal models which have been developed to date quite recapitulate human GBM establishment and progression (Schuhmacher & Squatrito, 2017).…”

Section: Discussionmentioning

confidence: 99%

“…Actually, the use of animal modeling is an excellent way to demonstrate the mechanisms involved in immune-editing, drug resistance, invasion, and metastasis. This allows for the examination of different therapies, which are designed to remove primary tumor cells as well as detached tumor initiated cells (also known as cancer stem cells; Schuhmacher & Squatrito, 2017). Thus, the similarity of models regarding tumor behavior, tumor invasion, and the affection manner on the brain function are very important concerns.…”

Section: Introductionmentioning

confidence: 99%

Neuropathological and genomic characterization of glioblastoma‐induced rat model: How similar is it to humans for targeted therapy?

Sharifzad

Yasavoli‐Sharahi

Mardpour

et al. 2019

Journal Cellular Physiology

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Glioblastoma multiforme (GBM) is a unique aggressive tumor and mostly develops in the brain, while rarely spreading out of the central nervous system. It is associated with a high mortality rate; despite tremendous efforts having been made for effective therapy, tumor recurrence occurs with high prevalence. To elucidate the mechanisms that lead to new drug discovery, animal models of tumor progression is one of the oldest and most beneficial approaches to not only investigating the aggressive nature of the tumor, but also improving preclinical research. It is also a useful tool for predicting novel therapies' effectiveness as well as side effects. However, there are concerns that must be considered, such as the heterogeneity of tumor, biological properties, pharma dynamic, and anatomic shapes of the models, which have to be similar to humans as much as possible. Although several methods and various species have been used for this approach, the real recapitulation of the human tumor has

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“…Animal models have provided some solutions to the limitations of these in vitro cultures by providing a more holistic system for dissecting GBM molecular and cellular biology by incorporating tumor-host interactions [ 13 ]. Of these models, genetically engineered mouse models have been particularly useful in understanding GBM but are limited by substantial differences between human and mouse brains [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Cerebral organoids: emerging ex vivo humanoid models of glioblastoma

Papaioannou

Sangster

Sajid

et al. 2020

acta neuropathol commun

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Glioblastoma is an aggressive form of brain cancer that has seen only marginal improvements in its bleak survival outlook of 12–15 months over the last forty years. There is therefore an urgent need for the development of advanced drug screening platforms and systems that can better recapitulate glioblastoma’s infiltrative biology, a process largely responsible for its relentless propensity for recurrence and progression. Recent advances in stem cell biology have allowed the generation of artificial tridimensional brain-like tissue termed cerebral organoids. In addition to their potential to model brain development, these reagents are providing much needed synthetic humanoid scaffolds to model glioblastoma’s infiltrative capacity in a faithful and scalable manner. Here, we highlight and review the early breakthroughs in this growing field and discuss its potential future role for glioblastoma research.

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Animal Models in Glioblastoma: Use in Biology and Developing Therapeutic Strategies

Cited by 4 publications

References 129 publications

Current Challenges and Opportunities in Treating Glioblastoma

Current Challenges and Opportunities in Treating Glioblastoma

Neuropathological and genomic characterization of glioblastoma‐induced rat model: How similar is it to humans for targeted therapy?

Cerebral organoids: emerging ex vivo humanoid models of glioblastoma

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