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REVIEW article

Front. Genet.
Sec. Cancer Genetics and Oncogenomics
Volume 15 - 2024 | doi: 10.3389/fgene.2024.1356611
This article is part of the Research Topic Glioma Immunotherapy Based on Single-cell Sequencing and Spatiotemporal Transcriptome View all articles

Cellular diversity through space and time: Adding new dimensions to GBM therapeutic development

Provisionally accepted
Amanda L. Johnson Amanda L. Johnson 1,2Hernando Lopez-Bertoni Hernando Lopez-Bertoni 1,3*
  • 1 Kennedy Krieger Institute, Baltimore, Maryland, United States
  • 2 School of Medicine, Johns Hopkins University, Baltimore, United States
  • 3 Johns Hopkins Medicine, Johns Hopkins University, Baltimore, Maryland, United States

The final, formatted version of the article will be published soon.

    The current median survival for glioblastoma (GBM) patients is only about 16 months, with many patients succumbing to the disease in just a matter of months, making it the most common and aggressive primary brain cancer in adults. This poor outcome is, in part, due to the lack of new treatment options with only one FDA-approved treatment in the last decade. Advances in sequencing techniques and transcriptomic analyses have revealed a vast degree of heterogeneity in GBM, from inter-patient diversity to intra-tumoral cellular variability. These cutting-edge approaches are providing new molecular insights highlighting a critical role for the tumor microenvironment (TME) as a driver of cellular plasticity and phenotypic heterogeneity. With this expanded molecular toolbox, the influence of TME factors, including endogenous (e.g., oxygen and nutrient availability and interactions with non-malignant cells) and iatrogenically induced (e.g., post-therapeutic intervention) stimuli, on tumor cell states can be explored to a greater depth.There exists a critical need for interrogating the temporal and spatial aspects of patient tumors at a high, cell-level resolution to identify therapeutically targetable states, interactions and mechanisms. In this review, we discuss advancements in our understanding of spatiotemporal diversity in GBM with an emphasis on the influence of hypoxia and immune cell interactions on tumor cell heterogeneity. Additionally, we describe specific high-resolution spatially resolved methodologies and their potential to expand the impact of pre-clinical GBM studies. Finally, we highlight clinical attempts at targeting hypoxia-and immune-related mechanisms of malignancy and the potential therapeutic opportunities afforded by single-cell and spatial exploration of GBM patient specimens.

    Keywords: Glioblastoma, single-cell sequencing, spatial omics, heterogeneity, Cellular plasticity, cancer therapeutics, Immunotherapy, hypoxia

    Received: 15 Dec 2023; Accepted: 15 Apr 2024.

    Copyright: © 2024 Johnson and Lopez-Bertoni. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Hernando Lopez-Bertoni, Kennedy Krieger Institute, Baltimore, MD 21205, Maryland, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.