Brain malignancies: Glioblastoma and brain metastases

Seminars in Cancer Biology, Journal Year: 2019, Volume and Issue: 60, P. 262 - 273

Published: Oct. 22, 2019

Brain, the major organ of central nervous system controls and processes most body activities. Therefore, aggressive brain tumor - glioblastoma metastases from other organs to are lethal leaving patients with very short time survival. The tissue landscape is different any tissues specific microenvironment, comprising stem cells niches blood-brain barrier, significantly influences low rate metastasis out brain, but better accommodates brain-invading cancer. In contrast frequency (0.5%) all metastases, 10%-45% primary cancers do metastasize brain. This review addresses general cellular molecular pathways that some extent similar in both types involving circulating (CTCs) cancer (CSCs) characteristics, metastatic niches. invasion a dynamic process reversible epithelial-to-mesenchymal (EMT) cell process, creating transient gradient state inter-connected epigenetic plasticity metastasizing (m)CSCs. These can switch between stationary, proliferating/dormant migratory, mesenchymal-like state. Settling their respective as dormant CSCs secondary common feature metastases. metastasis, malignant mGSC express markers mesenchymal GSC subtype (MES-GSC), such CD44 YK-40 obstacle seems be propagating various organs' microenvironments, home GSCs glioblastoma. Focusing on one stromal component niches, (MSCs), we report herein differential effects cells, highly depending genetic subtype. On hand, hindrance progression mCSCs seem crossing blood-brain-barrier. Novel therapeutic approaches for advancing slowly, trends involve targeting sub-clones selective determinants update four lung, breast, melanoma colorectal carcinoma presented.

Language: Английский

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Diffuse Glioma Heterogeneity and Its Therapeutic Implications

Cancer Discovery, Journal Year: 2021, Volume and Issue: 11(3), P. 575 - 590

Published: Feb. 8, 2021

Diffuse gliomas represent a heterogeneous group of universally lethal brain tumors characterized by minimally effective genotype-targeted therapies. Recent advances have revealed that remarkable level genetic, epigenetic, and environmental heterogeneity exists within each individual glioma. Together, these interconnected layers intratumoral result in extreme phenotypic at the cellular level, providing for multiple mechanisms therapeutic resistance forming highly adaptable resilient disease. In this review, we discuss how glioma malignant state plasticity drive to existing therapies look future which challenges may be overcome. SIGNIFICANCE: Glioma cell formidable hurdles development novel targeted However, convergence genotypically diverse cells into limited set epigenetically encoded transcriptional states present an opportunity strategy call "State Selective Lethality." approach, (as opposed genetic perturbations/mutations) are subject targeting, plasticity-mediated is minimized through design "trapping agents."

Language: Английский

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Glioblastoma Stem Cells: Driving Resilience through Chaos

Trends in cancer, Journal Year: 2020, Volume and Issue: 6(3), P. 223 - 235

Published: Feb. 3, 2020

Language: Английский

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Outer Radial Glia-like Cancer Stem Cells Contribute to Heterogeneity of Glioblastoma

Cell stem cell, Journal Year: 2020, Volume and Issue: 26(1), P. 48 - 63.e6

Published: Jan. 1, 2020

Glioblastoma is a devastating form of brain cancer. To identify aspects tumor heterogeneity that may illuminate drivers invasion, we created glioblastoma cell atlas with single-cell transcriptomics cancer cells mapped onto reference framework the developing and adult human brain. We find multiple GSC subtypes exist within single tumor. Within these GSCs, an invasive population similar to outer radial glia (oRG), fetal type expands stem niche in normal cortex. Using live time-lapse imaging primary resected tumors, discover tumor-derived oRG-like undergo characteristic mitotic somal translocation behavior previously only observed development, suggesting reactivation developmental programs. In addition, show PTPRZ1 mediates both invasion. These data suggest presence heterogeneous GSCs underlie glioblastoma's rapid progression

Language: Английский

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The landscape of the mesenchymal signature in brain tumours

Brain, Journal Year: 2019, Volume and Issue: 142(4), P. 847 - 866

Published: March 21, 2019

The complexity of glioblastoma multiforme, the most common and lethal variant gliomas, is reflected by cellular molecular heterogeneity at both inter- intra-tumoural levels. Molecular subtyping has arisen in past two decades as a promising strategy to give better predictions multiforme evolution, disease pathways, rational treatment options. Cancer Genome Atlas network initially identified four subtypes multiforme: proneural, neural, mesenchymal classical. However, further studies, also investigated glioma stem cells, have only three subtypes: proneural-mesenchymal transition upon tumour recurrence been suggested mechanism resistance radiation chemotherapy treatment. Glioblastoma patients with subtype tend survive shorter than other when analysis restricted samples low transcriptional heterogeneity. Although signature malignant may seem odds idea ectodermal origin neural-glial lineages, presence supported several studies suggesting that it can result from: (i) intrinsic expression cells affected accumulated genetic mutations cell origin; (ii) micro-environments recruited macrophages or microglia, pericytes, progenitors; (iii) treatment, including radiotherapy, antiangiogenic therapy possibly chemotherapy. Genetic abnormalities, mainly NF1 mutations, together NF-κB programs, are main driver acquiring mesenchymal-signature. This far from being simply tissue artefacts, single glioma, circulating released micro-environment. All these suggest induced sustained via mechanisms micro-environment factors. poorer prognosis, they favourable response immunotherapy intensive radio-

Language: Английский

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