Mesenchymal Transformation: The Rosetta Stone of Glioblastoma Pathogenesis and Therapy Resistance.

in Advanced science (Weinheim, Baden-Wurttemberg, Germany) by Zulfikar Azam, Shing-Shun Tony To, Bakhos A Tannous

TLDR

  • The study is about understanding how the brain tumor called glioblastoma (GBM) changes over time and how the environment around it affects these changes. The authors found that different parts of the tumor can have different characteristics, and that these parts can change in response to treatments or when the tumor comes back. The study also found that the environment around the tumor can influence these changes. The authors suggest that future research should focus on finding new ways to treat GBM that take into account these changes and the environment around the tumor.

Abstract

Despite decades of research, glioblastoma (GBM) remains invariably fatal among all forms of cancers. The high level of inter- and intratumoral heterogeneity along with its biological location, the brain, are major barriers against effective treatment. Molecular and single cell analysis identifies different molecular subtypes with varying prognosis, while multiple subtypes can reside in the same tumor. Cellular plasticity among different subtypes in response to therapies or during recurrence adds another hurdle in the treatment of GBM. This phenotypic shift is induced and sustained by activation of several pathways within the tumor itself, or microenvironmental factors. In this review, the dynamic nature of cellular shifts in GBM and how the tumor (immune) microenvironment shapes this process leading to therapeutic resistance, while highlighting emerging tools and approaches to study this dynamic double-edged sword are discussed.

Overview

  • The study focuses on the dynamic nature of cellular shifts in glioblastoma (GBM) and how the tumor (immune) microenvironment shapes this process leading to therapeutic resistance. The authors discuss the molecular and single cell analysis that identifies different molecular subtypes with varying prognosis, while multiple subtypes can reside in the same tumor. They also highlight the cellular plasticity among different subtypes in response to therapies or during recurrence, which is induced and sustained by activation of several pathways within the tumor itself or microenvironmental factors. The primary objective of the study is to provide a comprehensive review of the dynamic nature of cellular shifts in GBM and the role of the tumor (immune) microenvironment in shaping this process, leading to therapeutic resistance. The authors also discuss emerging tools and approaches to study this dynamic double-edged sword.

Comparative Analysis & Findings

  • The study does not provide a direct comparative analysis of outcomes under different experimental conditions or interventions. However, it highlights the molecular and single cell analysis that identifies different molecular subtypes with varying prognosis, while multiple subtypes can reside in the same tumor. The authors also discuss the cellular plasticity among different subtypes in response to therapies or during recurrence, which is induced and sustained by activation of several pathways within the tumor itself or microenvironmental factors. The key findings of the study are that the dynamic nature of cellular shifts in GBM is a major barrier against effective treatment, and the tumor (immune) microenvironment plays a crucial role in shaping this process leading to therapeutic resistance. The authors also discuss emerging tools and approaches to study this dynamic double-edged sword.

Implications and Future Directions

  • The study's findings highlight the importance of understanding the dynamic nature of cellular shifts in GBM and the role of the tumor (immune) microenvironment in shaping this process leading to therapeutic resistance. The authors suggest that future research should focus on developing novel therapeutic strategies that target the dynamic nature of cellular shifts in GBM and the tumor (immune) microenvironment. They also suggest that emerging tools and approaches, such as single cell analysis and immunotherapy, could be used to study this dynamic double-edged sword. The study's findings also highlight the need for further research to identify the specific pathways and factors that induce and sustain cellular plasticity in GBM and the tumor (immune) microenvironment. The authors also suggest that future research should focus on developing personalized treatment strategies that take into account the molecular and cellular heterogeneity of GBM and the tumor (immune) microenvironment.
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