The literature contains over 3000 publications retrieval in MEDLINE with the term ? glioblastoma? in the title and many more if related terms and fields are used. This topic has been discussed comprehensively in a recent book cancer of the nervous system (1). This special issue of TCRT contains papers from leading experts on research in brain tumors and are considered to be important contributions. Gains in understanding the molecular biology of GBM and availability of new molecular technologies has brightened the prospects of cure of GBM. There are several success stories in treatment of other cancers, but characteristics of GBM that hinder efforts to cure it include the following:

? Access of chemotherapy to the tumor is more restricted than to other organs due to the blood-brain barrier.
? Aggressive local spread of the tumor.
? Location of the tumor within the brain obviates radical extirpation.
? Regardless of the amount of the tumor destroyed, the residual tumor grows rapidly.

Cure of GBM is unlikely unless the tumor is eradicated completely. The ideal treatment of GBM should have the following characteristics:

? Selective action against the tumor while sparing normal brain cells.
? Combination of a diagnostic with the therapeutic agent so that the treatment progress can be followed from start to the end.
? Action of the therapeutic agent should be continuous or the administration should be repeatable until the tumor is eradicated completely. Once this is achieved, the treatment should be terminable.
? The treatment should take into consideration the heterogeneous nature of the disease, which makes it unlikely that a uniform approach would be suitable for all patients; rather it should be tailored for individual patients.
? Currently no single agent is available and effort should be made to find the best combination from several treatments available.

The doses and durations of treatment with currently available chemotherapeutic and radiotherapeutic agents usually have an upper limit although some measures are available to extend the limits. Viral vector-mediated gene therapy is usually not repeatable. Therapy with short interfering RNAs (siRNAs) delivered by nonviral vectors may be repeatable.

One of the promising approaches at research stage is use of genetically modified bacteria for selective destruction of GBM as an adjunct to surgery. Knowledge of genomes of various bacterial candidates and established technologies for genetic modification of bacteria make this tool practical. Genetically modified bacteria can be introduced into and maintained in the tumor until it is completely destroyed. After the destruction is verified, bacteria can be eliminated by an appropriate antibiotic. Although the safety of this approach needs to be established, it is likely to be more effective and safer than use of oncolytic viruses.

With several approaches available and the rapid progress that is being made, it is hoped that there will be some breakthrough in the quest for cure of GBM in the next decade. Regardless of which strategy proves to be most effective, the approach to management of GBM will most likely be personalized. This is in keeping with the trend in personalized medicine in general and therapy of cancer in particular.

Reference

1. Black, P. M., Loeffler, J. (Eds) Cancer of the Nervous System, 2nd Ed. Lippincott, Williams & Wilkins, Philadelphia (2005).

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