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EGFR-dependent mechanisms in glioblastoma: towards a better therapeutic strategy

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Abstract

Glioblastoma is a particularly resilient cancer, and while therapies may be able to reach the brain by crossing the blood–brain barrier, they then have to deal with a highly invasive tumor that is very resistant to DNA damage. It seems clear that in order to kill aggressive glioma cells more efficiently and with fewer side effects on normal tissue, there must be a shift from classical cytotoxic chemotherapy to more targeted therapies. Since the epidermal growth factor receptor (EGFR) is altered in almost 50 % of glioblastomas, it currently represents one of the most promising therapeutic targets. In fact, it has been associated with several distinct steps in tumorigenesis, from tumor initiation to tumor growth and survival, and also with the regulation of cell migration and angiogenesis. However, inhibitors of the EGFR kinase have produced poor results with this type of cancer in clinical trials, with no clear explanation for the tumor resistance observed. Here we will review what we know about the expression and function of EGFR in cancer and in particular in gliomas. We will also evaluate which are the possible molecular and cellular escape mechanisms. As a result, we hope that this review will help improve the design of future EGFR-targeted therapies for glioblastomas.

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Acknowledgments

The work in the authors’ laboratory is funded by the Spanish Ministerio de Economía y Competitividad (Instituto de Salud Carlos III: PI12/00775 and RD12/0036/0027). We thank Angel Ayuso-Sacido and Juan Sepúlveda-Sánchez for their critical review of the manuscript.

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  1. Neuro-Oncology Unit, Instituto de Salud Carlos III-UFIEC, Madrid, Spain

    Cristina Zahonero & Pilar Sánchez-Gómez

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  1. Cristina Zahonero
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  2. Pilar Sánchez-Gómez
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Correspondence to Pilar Sánchez-Gómez.

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Zahonero, C., Sánchez-Gómez, P. EGFR-dependent mechanisms in glioblastoma: towards a better therapeutic strategy. Cell. Mol. Life Sci. 71, 3465–3488 (2014). https://doi.org/10.1007/s00018-014-1608-1

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  • DOI: https://doi.org/10.1007/s00018-014-1608-1

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