Vector therapies for malignant glioma: shifting the clinical paradigm

Abstract

Background: Malignant glioma represents one of the most aggressive and devastating forms of human cancer. At present, there exists no successful treatment for this disease. Gene therapy, or vector therapy, has emerged as a viable experimental treatment method for intracranial malignancies. Objective: Vector therapy paradigms that have entered the clinical arena have shown adequate safety; however, the majority of the studies failed to observe significant clinical benefits. As such, researchers have refocused their efforts on developing novel vectors as well as new delivery methods to enhance the therapeutic effect of a particular vector. In this review, we discuss common vector therapy approaches used in clinical trials, their drawbacks and potential ways of overcoming these challenges. Methods: We focus on the experimental evaluation of cell-based vector therapies and adenoviral and herpes simplex virus type 1 vectors in the treatment of malignant glioma. Conclusion: Vector therapy remains a promising treatment strategy for malignant glioma. Although significant questions remain to be answered, early clinical data suggest safety of this approach and future studies will likely address the efficacy of the proposed therapy.

Keywords::

• adenovirus
• brain tumor
• cancer
• clinical trial
• gene therapy
• glioma
• herpes simplex virus type 1
• MRI
• PET
• vector therapy

Acknowledgements

This work was supported by the National Cancer Institute (R01CA122930), the National Institute of Neurological Disorders and Stroke (K08-NS046430), the Alliance for Cancer Gene Therapy and the American Cancer Society (RSG-07-276-01-MGO).

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