Emerging therapeutic targets for glioblastoma multiform

Abstract

Current treatments for glioblastoma, the most common primary malignant tumour, have not been successful in curing the disease. About 65 new therapies that are in development have been reviewed to identify the most promising targets for drug development. These include antineoplastic compounds, drugs which have novel mechanisms of action to either inhibit tumour growth or to destroy the tumour. Other methods in development are refinements of radiotherapy. Novel approaches include immunological approaches (such as brain tumour vaccines), anti-angiogenic agents, protection against the adverse effects of high dose chemotherapy, agents to sensitise tumours to radiation therapy and gene therapy. Gene therapy with herpes simplex virus (HSV)-thymidine kinase combined with ganciclovir had raised high hopes only to prove ineffective in Phase III clinical trials. Newer modifications of gene therapy include use of adenoviral vectors and new or improved prodrug/suicide systems, gene replacement approaches, or strategies targeting the immune response or tumour angiogenesis. Various antisense approaches are also in development. It is unlikely that any of these approaches or combination of them will eradicate these tumours as complete extirpation of the tumours is not the goal of any of the therapies in development. Unless these tumours are eradicated completely, it is impossible to cure them. Complete extirpation and not merely reduction in size of the tumour should be the criteria for a product to proceed to human clinical trials. The only feasible method to achieve this is to supplement surgery with a genetically modified bacterium to eradicate the residual tumour.

• anti-angiogenic therapy
• antibrain tumour cytotoxin
• antineoplastic agents
• antisense therapy
• biodegradable polymers
• brain cancer
• brain tumour
• brain tumour vaccine
• chemosensitisation
• chemotherapy
• gene therapy
• glioblastoma multiform
• immunotherapy
• monoclonal antibody (mAb)
• oligodeoxynucleotides
• oncolysis
• radiotherapy
• rat glioma model
• signal transduction pathways
• viral vectors