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Drosophila melanogaster as a Model System for Human Glioblastomas

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The Drosophila Model in Cancer

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1167))

Abstract

Glioblastoma multiforme (GBM) is the most common primary malignant adult brain tumor. Genomic amplifications, activating mutations, and overexpression of receptor tyrosine kinases (RTKs) such as EGFR, and genes in core RTK signaling transduction pathways such as PI3K are common in GBM. However, efforts to target these pathways have been largely unsuccessful in the clinic, and the median survival of GBM patients remains poor at 14–15 months. Therefore, to improve patient outcomes, there must be a concerted effort to elucidate the underlying biology involved in GBM tumorigenesis. Drosophila melanogaster has been a highly effective model for furthering our understanding of GBM tumorigenesis due to a number of experimental advantages it has over traditional mouse models. For example, there exists extensive cellular and genetic homology between humans and Drosophila, and 75% of genes associated with human disease have functional fly orthologs. To take advantage of these traits, we developed a Drosophila GBM model with constitutively active variants of EGFR and PI3K that effectively recapitulated key aspects of GBM disease. Researchers have utilized this model in forward genetic screens and have expanded on its functionality to make a number of important discoveries regarding requirements for key components in GBM tumorigenesis, including genes and pathways involved in extracellular matrix signaling, glycolytic metabolism, invasion/migration, stem cell fate and differentiation, and asymmetric cell division. Drosophila will continue to reveal novel biological pathways and mechanisms involved in gliomagenesis, and this knowledge may contribute to the development of effective treatment strategies to improve patient outcomes.

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Acknowledgements

We thank Dr. Nathaniel H. Boyd and Hye Rim Kim for critical reading of this manuscript.

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Authors and Affiliations

  1. Department of Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, GA, USA

    Alexander S. Chen & Renee D. Read

  2. Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, USA

    Renee D. Read

  3. Winship Cancer Center, Emory University School of Medicine, Atlanta, GA, USA

    Renee D. Read

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  1. Department of Biochemistry and Molecular Biology, Tulane Cancer Center, LCRC, Tulane University School of Medicine, New Orleans, LA, USA

    Wu-Min Deng

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Chen, A.S., Read, R.D. (2019). Drosophila melanogaster as a Model System for Human Glioblastomas. In: Deng, WM. (eds) The Drosophila Model in Cancer. Advances in Experimental Medicine and Biology, vol 1167. Springer, Cham. https://doi.org/10.1007/978-3-030-23629-8_12

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