J Neurol Neurosurg Psychiatry 84:213-222 doi:10.1136/jnnp-2012-302946
  • Neuro-oncology
  • Review

The art of gene therapy for glioma: a review of the challenging road to the bedside

Editor's Choice
  1. Maciej S Lesniak
  1. The Brain Tumour Center, The University of Chicago, Chicago, Illinois, USA
  1. Correspondence to Dr Maciej S Lesniak, The Brain Tumour Center, The University of Chicago, 5841 South Maryland Ave, MC 3026, Chicago, IL 60637, USA; mlesniak{at}
  1. Contributors AT wrote and organised the manuscript. AA summarised the data on current gene therapy trials. K-SM provided an overview on current challenges. MSL read, reviewed, funded and approved the final review for submission.

  • Received 10 April 2012
  • Revised 16 July 2012
  • Accepted 23 July 2012
  • Published Online First 19 September 2012


Glioblastoma multiforme (GBM) is a highly invasive brain tumour that is unvaryingly fatal in humans despite even aggressive therapeutic approaches such as surgical resection followed by chemotherapy and radiotherapy. Unconventional treatment options such as gene therapy provide an intriguing option for curbing glioma related deaths. To date, gene therapy has yielded encouraging results in preclinical animal models as well as promising safety profiles in phase I clinical trials, but has failed to demonstrate significant therapeutic efficacy in phase III clinical trials. The most widely studied antiglioma gene therapy strategies are suicide gene therapy, genetic immunotherapy and oncolytic virotherapy, and we have attributed the challenging transition of these modalities into the clinic to four major roadblocks: (1) anatomical features of the central nervous system, (2) the host immune system, (3) heterogeneity and invasiveness of GBM and (4) limitations in current GBM animal models. In this review, we discuss possible ways to jump these hurdles and develop new gene therapies that may be used alone or in synergy with other modalities to provide a powerful treatment option for patients with GBM.


  • Funding Research by the authors was supported by the NCI (R01CA122930, R01CA138587), the National Institute of Neurological Disorders and Stroke (U01NS069997) and the American Cancer Society (RSG-07-276-01-MGO).

  • Competing interests None.

  • Provenance and peer review Commissioned; externally peer reviewed.

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