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Glioblastoma heterogeneity and the tumour microenvironment: implications for preclinical research and development of new treatments.
Biochem Soc Trans 2019; 47(2):625-638BS

Abstract

Glioblastoma is the deadliest form of brain cancer. Aside from inadequate treatment options, one of the main reasons glioblastoma is so lethal is the rapid growth of tumour cells coupled with continuous cell invasion into surrounding healthy brain tissue. Significant intra- and inter-tumour heterogeneity associated with differences in the corresponding tumour microenvironments contributes greatly to glioblastoma progression. Within this tumour microenvironment, the extracellular matrix profoundly influences the way cancer cells become invasive, and changes to extracellular (pH and oxygen levels) and metabolic (glucose and lactate) components support glioblastoma growth. Furthermore, studies on clinical samples have revealed that the tumour microenvironment is highly immunosuppressive which contributes to failure in immunotherapy treatments. Although technically possible, many components of the tumour microenvironment have not yet been the focus of glioblastoma therapies, despite growing evidence of its importance to glioblastoma malignancy. Here, we review recent progress in the characterisation of the glioblastoma tumour microenvironment and the sources of tumour heterogeneity in human clinical material. We also discuss the latest advances in technologies for personalised and in vitro preclinical studies using brain organoid models to better model glioblastoma and its interactions with the surrounding healthy brain tissue, which may play an essential role in developing new and more personalised treatments for this aggressive type of cancer.

Authors+Show Affiliations

Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, Australia.Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, Australia. Adelaide Medical School, Faculty of Health Sciences, University of Adelaide, Adelaide, Australia.SA Pathology, Royal Adelaide Hospital, Adelaide, Australia.Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, Australia. Adelaide Medical School, Faculty of Health Sciences, University of Adelaide, Adelaide, Australia. Cancer Clinical Trials Unit, Royal Adelaide Hospital, Adelaide, Australia.Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, Australia lisa.ebert@sa.gov.au mariana.oksdathmansilla@unisa.edu.au guillermo.gomez@unisa.edu.au.Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, Australia lisa.ebert@sa.gov.au mariana.oksdathmansilla@unisa.edu.au guillermo.gomez@unisa.edu.au.Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, Australia lisa.ebert@sa.gov.au mariana.oksdathmansilla@unisa.edu.au guillermo.gomez@unisa.edu.au.

Pub Type(s)

Journal Article
Review
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30902924

Citation

Perrin, Sally L., et al. "Glioblastoma Heterogeneity and the Tumour Microenvironment: Implications for Preclinical Research and Development of New Treatments." Biochemical Society Transactions, vol. 47, no. 2, 2019, pp. 625-638.
Perrin SL, Samuel MS, Koszyca B, et al. Glioblastoma heterogeneity and the tumour microenvironment: implications for preclinical research and development of new treatments. Biochem Soc Trans. 2019;47(2):625-638.
Perrin, S. L., Samuel, M. S., Koszyca, B., Brown, M. P., Ebert, L. M., Oksdath, M., & Gomez, G. A. (2019). Glioblastoma heterogeneity and the tumour microenvironment: implications for preclinical research and development of new treatments. Biochemical Society Transactions, 47(2), pp. 625-638. doi:10.1042/BST20180444.
Perrin SL, et al. Glioblastoma Heterogeneity and the Tumour Microenvironment: Implications for Preclinical Research and Development of New Treatments. Biochem Soc Trans. 2019 04 30;47(2):625-638. PubMed PMID: 30902924.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Glioblastoma heterogeneity and the tumour microenvironment: implications for preclinical research and development of new treatments. AU - Perrin,Sally L, AU - Samuel,Michael S, AU - Koszyca,Barbara, AU - Brown,Michael P, AU - Ebert,Lisa M, AU - Oksdath,Mariana, AU - Gomez,Guillermo A, Y1 - 2019/03/22/ PY - 2018/11/15/received PY - 2019/02/25/revised PY - 2019/02/28/accepted PY - 2019/3/25/pubmed PY - 2019/3/25/medline PY - 2019/3/24/entrez KW - brain organoids KW - clinical trials KW - glioblastoma KW - patient-derived tumour biopsies KW - tumour microenvironment SP - 625 EP - 638 JF - Biochemical Society transactions JO - Biochem. Soc. Trans. VL - 47 IS - 2 N2 - Glioblastoma is the deadliest form of brain cancer. Aside from inadequate treatment options, one of the main reasons glioblastoma is so lethal is the rapid growth of tumour cells coupled with continuous cell invasion into surrounding healthy brain tissue. Significant intra- and inter-tumour heterogeneity associated with differences in the corresponding tumour microenvironments contributes greatly to glioblastoma progression. Within this tumour microenvironment, the extracellular matrix profoundly influences the way cancer cells become invasive, and changes to extracellular (pH and oxygen levels) and metabolic (glucose and lactate) components support glioblastoma growth. Furthermore, studies on clinical samples have revealed that the tumour microenvironment is highly immunosuppressive which contributes to failure in immunotherapy treatments. Although technically possible, many components of the tumour microenvironment have not yet been the focus of glioblastoma therapies, despite growing evidence of its importance to glioblastoma malignancy. Here, we review recent progress in the characterisation of the glioblastoma tumour microenvironment and the sources of tumour heterogeneity in human clinical material. We also discuss the latest advances in technologies for personalised and in vitro preclinical studies using brain organoid models to better model glioblastoma and its interactions with the surrounding healthy brain tissue, which may play an essential role in developing new and more personalised treatments for this aggressive type of cancer. SN - 1470-8752 UR - https://www.unboundmedicine.com/medline/citation/30902924/Glioblastoma_heterogeneity_and_the_tumour_microenvironment:_implications_for_preclinical_research_and_development_of_new_treatments_ L2 - https://portlandpress.com/biochemsoctrans/article-lookup/doi/10.1042/BST20180444 DB - PRIME DP - Unbound Medicine ER -