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Heterogeneity of epidermal growth factor receptor signalling networks in glioblastoma

Nature Reviews Cancer volume 15, pages 302–310 (2015)Cite this article

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Abstract

As tumours evolve, the daughter cells of the initiating cell often become molecularly heterogeneous and develop different functional properties and therapeutic vulnerabilities. In glioblastoma (GBM), a lethal form of brain cancer, the heterogeneous expression of the epidermal growth factor receptor (EGFR) poses a substantial challenge for the effective use of EGFR-targeted therapies. Understanding the mechanisms that cause EGFR heterogeneity in GBM should provide better insights into how they, and possibly other amplified receptor tyrosine kinases, affect cellular signalling, metabolism and drug resistance.

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Figure 1: Multiple mechanisms regulate the development, progression and maintenance of tumour heterogeneity.
Figure 2: Receptor tyrosine kinase genetic alterations in primary glioblastoma.
Figure 3: Single-cell heterogeneity of receptor tyrosine kinase DNA, RNA and protein in glioblastoma.
Figure 4: Interlacing mechanisms shape intratumoural receptor tyrosine kinase heterogeneity during glioblastoma progression.
Figure 5: Impact of intratumoural receptor tyrosine kinase heterogeneity on the response to therapy in glioblastoma.

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Acknowledgements

This work is supported by grants from National Institute for Neurological Diseases and Stroke (NS73831 and NS080939-01), the National Cancer Institute (CA151819), The Ben and Catherine Ivy Foundation, the Defeat GBM Program of the National Brain Tumour Society and donations from the Ziering Family Foundation in memory of Sigi Ziering. W.K.C. is a fellow of the National Foundation for Cancer Research. The authors acknowledge the reading and comments by members of the Mischel laboratory.

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Authors and Affiliations

  1. Ludwig Institute for Cancer Research and the Department of Pathology, University of California San Diego, La Jolla, 92093, California, USA

    Frank B. Furnari & Paul S. Mischel

  2. Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, 90095, California, USA

    Timothy F. Cloughesy

  3. Ludwig Institute for Cancer Research and the Department of Medicine, University of California San Diego, La Jolla, 92093, California, USA

    Webster K. Cavenee

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Correspondence to Paul S. Mischel.

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Furnari, F., Cloughesy, T., Cavenee, W. et al. Heterogeneity of epidermal growth factor receptor signalling networks in glioblastoma. Nat Rev Cancer 15, 302–310 (2015). https://doi.org/10.1038/nrc3918

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