Journal
FRONTIERS IN ONCOLOGY
Volume 11, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2021.703764
Keywords
glioblastoma multiforme; heterogeneity; tumor microenvironment; dynamic; spatial resolution; deep learning; precision oncology
Categories
Funding
- National Institutes of Health/National Institute of Neurological Disorders & Stroke (NIH/NINDS) [R21-NS091555, R37-NS094804, R01-NS074387, R01-NS076991, R01-NS082311, R01-NS096756]
- Rogel Cancer Center Scholar Award
- Forbes Senior Research Scholar Award
- National institutes of Health/National Institute of Biomedical Imaging and Bioengineering (NIH/NIBIB) [R01-EB022563]
- University of Michigan MCube
- Department of Neurosurgery
- University of Michigan Rogel Comprehensive Cancer Center
- Pediatric Brain Tumor Foundation (BTF)
- Ian's Friends Foundation
- Leah's Happy Hearts Foundation
- Chad Tough Foundation
- Biosciences Initiative in Brain Cancer
- [UL1 TR002240]
- [F049768]
Ask authors/readers for more resources
Glioblastomas are the most common and aggressive tumors of the central nervous system, characterized by heterogeneity at histological, cellular, genomic, and dynamic levels. This heterogeneity is suggested to arise from organized and dynamic attributes, favoring malignancy and influencing treatment regimens.
Glioblastomas (GBM) are the most common and aggressive tumors of the central nervous system. Rapid tumor growth and diffuse infiltration into healthy brain tissue, along with high intratumoral heterogeneity, challenge therapeutic efficacy and prognosis. A better understanding of spatiotemporal tumor heterogeneity at the histological, cellular, molecular, and dynamic levels would accelerate the development of novel treatments for this devastating brain cancer. Histologically, GBM is characterized by nuclear atypia, cellular pleomorphism, necrosis, microvascular proliferation, and pseudopalisades. At the cellular level, the glioma microenvironment comprises a heterogeneous landscape of cell populations, including tumor cells, non-transformed/reactive glial and neural cells, immune cells, mesenchymal cells, and stem cells, which support tumor growth and invasion through complex network crosstalk. Genomic and transcriptomic analyses of gliomas have revealed significant inter and intratumoral heterogeneity and insights into their molecular pathogenesis. Moreover, recent evidence suggests that diverse dynamics of collective motion patterns exist in glioma tumors, which correlate with histological features. We hypothesize that glioma heterogeneity is not stochastic, but rather arises from organized and dynamic attributes, which favor glioma malignancy and influences treatment regimens. This review highlights the importance of an integrative approach of glioma histopathological features, single-cell and spatially resolved transcriptomic and cellular dynamics to understand tumor heterogeneity and maximize therapeutic effects.
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