Glioblastoma subtypes revisited

Sidaway, Peter

doi:10.1038/nrclinonc.2017.122

Cited by 61 publications

(57 citation statements)

References 1 publication

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“…Since the advent of the current standard therapy for newly diagnosed GBM consisting of surgical resection and chemoradiotherapy, there have been no major treatment advances, with the possible exception of mitosis-disrupting tumor-treating fields (TTFields) (Geraldo et al, 2019). New insights into the inter- and intra-tumoral genetic heterogeneity of GBM (Patel et al, 2014; Sidaway, 2017) highlight the likely futility of discovering tumor cell-targeted therapies with therapeutic impact on sufficient patients, or on sufficient tumor cells within the tumor mass. Nevertheless, we argue that there is one common feature of GBM that can be potentially targeted: the massive infiltrate of microglia and macrophages.…”

Section: Resultsmentioning

confidence: 99%

“…It also contains cancer stem cells (CSCs), which contribute to tumor initiation and therapeutic resistance (Lathia et al, 2015). According to gene expression profiling based on data from The Cancer Genome Atlas (TCGA) 1 , there are three molecular subtypes of GBM defined, including proneural, classical and mesenchymal (Verhaak et al, 2010; Sidaway, 2017). These subtypes are characterized by the patterns of alterations of the EGFR , NF1 , PDGFRA and IDH1 genes, in addition to their response to therapy (Crespo et al, 2015; Verhaak et al, 2010).…”

Section: Tumor-associated Microglia and Macrophages In Glioblastomamentioning

confidence: 99%

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Harnessing Microglia and Macrophages for the Treatment of Glioblastoma

et al. 2019

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Glioblastoma multiforme (GBM) is the most malignant form of brain tumors, with a dismal prognosis. During the course of the disease, microglia and macrophages both infiltrate the tumor microenvironment and contribute considerably in glioma development. Thus, tumor-associated microglia and macrophages have recently emerged as potentially key therapeutic targets. Here, we review the physiology of microglia and their responses in brain cancer. We further discuss current treatment options for GBM using radiotherapy, and novel advances in our knowledge of microglia physiology, with emphasis on the recently discovered pathway that controls the baseline motility of microglia processes. We argue that the latter pathway is an interesting therapeutic avenue to pursue for the treatment of glioblastoma.

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Section: Resultsmentioning

confidence: 99%

Section: Tumor-associated Microglia and Macrophages In Glioblastomamentioning

confidence: 99%

Harnessing Microglia and Macrophages for the Treatment of Glioblastoma

et al. 2019

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“…GBM is also a remarkably heterogeneous tumor that facilitates immune escape, which may be the largest obstacle (13,76,77). According to the gene expression analysis, GBM can be divided into four subtypes: typical, neuroural, proneural, and mesocytic (78). Even within the same tumor specimen, GBM showed significant heterogeneity.…”

Section: Heterogeneity Of Gbm and Antigen Escapementioning

confidence: 99%

Chimeric Antigen Receptor T-Cell Therapy in Glioblastoma: Current and Future

et al. 2020

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Glioblastoma (GBM) is a highly aggressive glioma with an extremely poor prognosis after conventional treatment. Recent advances in immunotherapy offer hope for these patients with incurable GBM. Our present review aimed to provide an overview of immunotherapy for GBM, especially chimeric antigen receptor T-cell (CAR T) therapy. CAR T-cell immunotherapy, which involves the engineering of T cells to kill tumors by targeting cell surface-specific antigens, has been successful in eliminating B-cell leukemia by targeting CD19. IL-13Ra2, EGFRvIII, and HER2-targeted CAR T cells have shown significant clinical efficacy and safety in phase 1 or 2 clinical trials conducted in patients with GBM; these findings support the need for further studies to examine if this therapy can ultimately benefit this patient group. However, local physical barriers, high tumor heterogeneity, and antigen escape make the use of CAR T therapy, as a treatment for GBM, challenging. The potential directions for improving the efficacy of CAR T in GBM are to combine the existing traditional therapies and the construction of multi-target CAR T cells.

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“…Extensive efforts have been undertaken to define the transcriptional programmes of brain tumours [33-35]. Integrating these datasets with enhancer maps and TF predictions can provide additional insight about key TFs that regulate tumour gene expression programmes and cellular heterogeneity.…”

Section: Reverse‐engineering Enhancers To Characterize Transcription mentioning

confidence: 99%

Invited Review: The role and contribution of transcriptional enhancers in brain cancer

Arabzade

Stuckert

Bertrand

et al. 2020

Neuropathology Appl Neurobio

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2020) Neuropathology and Applied Neurobiology 46, 48-56 The role and contribution of transcriptional enhancers in brain cancer Genetic alterations identified across several paediatric and adult brain tumours reveal recurrent disruption of active chromatin landscapes and dysregulation of transcriptional programmes. Noncoding elements, specifically enhancers, are central to these mechanisms, and are influenced by developmental and neural gene regulatory signatures. Epigenomic and transcriptomic methods and techniques have facilitated detection of active enhancers, and characterization of brain tumours integrated with genomic structural information. These datasets have provided new insights into the mechanisms of transcriptional control that are profoundly altered in childhood and adult brain cancer; offering new ideas and molecular targets for therapeutic intervention. This review summarizes recent advances in our understanding of active transcriptional programmes of brain cancer, their impact on tumour development, and research areas for further exploration.

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Glioblastoma subtypes revisited

Cited by 61 publications

References 1 publication

Harnessing Microglia and Macrophages for the Treatment of Glioblastoma

Harnessing Microglia and Macrophages for the Treatment of Glioblastoma

Chimeric Antigen Receptor T-Cell Therapy in Glioblastoma: Current and Future

Invited Review: The role and contribution of transcriptional enhancers in brain cancer

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