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The art of gene therapy for glioma: a review of the challenging road to the bedside
  1. Alex Tobias,
  2. Atique Ahmed,
  3. Kyung-Sub Moon,
  4. 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}surgery.bsd.uchicago.edu

Abstract

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.

  • Glioblastoma multiforme (GBM)
  • gene therapy
  • clinical trial
  • synergy
  • imaging
  • neurooncology
  • neurosurgery
  • neuroimmunology
  • neurovirology
  • molecular biology

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Footnotes

  • 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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