Glioblastoma is the most common form of primary brain cancer and remains one of the most aggressive forms of human cancer. Current standard of care involves maximal surgical resection followed by concurrent therapy with radiation and the DNA alkylating agent temozolomide. Despite this aggressive regimen, the median survival remains approximately 14 months. Meaningful strategies for therapeutic intervention are desperately needed. Development of such strategies will require an understanding of the therapeutic concepts that have evolved over the past three decades. This article reviews the key principles that drive the formulation of therapeutic strategies in glioblastoma. Specifically, the concepts of tumour heterogeneity, oncogene addiction, non-oncogene addiction, tumour initiating cells, tumour microenvironment, non-coding sequences and DNA damage response will be reviewed.
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Funding This work was supported by the Doris Duke Charitable Foundation Clinical Scientist Development Award, the Sontag Foundation Distinguished Scientist Award, the Burroughs Wellcome Fund Career Awards for Medical Sciences, the Kimmel Scholar award, a Discovery Grant from the American Brain Tumour Association, a National Cancer Institute K12 award, the Danish National Research Foundation, the Czech Ministry of Health (NT/11065-5/2010), and the European Commission (projects DDResponse, CZ.1.05/2.1.00/01.0030, and Infla-Care).
Competing interests None.
Provenance and peer review Commissioned; externally peer reviewed.
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