Key concepts in glioblastoma therapy
- 1Department of Neurosurgery, Karolinska University Hospital, Stockholm, Sweden
- 2Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
- 3Danish Cancer Society Research Center, Copenhagen, Denmark
- 4Laboratory of Genome Integrity and Institute of Molecular and Translational Medicine, Palacky University, Olomouc, Czech Republic
- 5Department of Neurosurgery, Rigshospitalet, Copenhagen, Denmark
- 6Center for Theoretical and Applied Neurosurgery, UCSD, San Diego, California, USA
- 7Division of Neurosurgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
- Correspondence to Dr Clark C Chen, Director of Clinical Neuro-oncology, Attending Neurosurgeon, Beth Israel Deaconess Medical Center, Department of Radiation Oncology, Division of Genomic Stability and DNA Repair, Dana-Farber Cancer Institute, Jimmy Fund 620A, 44 Binney Street, Boston, MA 02115-6084, USA;
Contributors CCC and KN authored the sections on tumour heterogeneity (concept 1), oncogene addiction (concept 2), non-oncogene addiction (concept 3), non-coding RNAs (concept 6). CCC, BJ and BJ Jr authored the section on tumour initiating cells (concept 4) and DNA damage response (concept 7) and CCC, WF, BC and BJ Jr authored the section on tumour microenvironment (concept 5). The content of the final manuscript was reviewed by all the authors.
- Received 8 June 2011
- Revised 14 November 2011
- Accepted 24 January 2012
- Published Online First 6 March 2012
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.
- targeted therapy
- oncogene addiction
- non-oncogene addiction
- tumour-initiating cells
- non-coding sequences
- DNA damage response
- molecular biology
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.