Gene therapy strategies for intracranial tumours: glioma and pituitary adenomas

Intracranial tumours such as brain gliomas and pituitary adenomas pose a ch allenging area of research for the development of gene therapy strategies, both from the point of view of the severity of the diseases, to the physiol ogical implication of gene delivery into the central nervous system and pit uitary gland. On the one hand, brain gliomas are very malignant tumours, wi th a life expectancy of six months to a year at the most after the time of diagnosis, in spite of advances in treatment modalities which involve chemo therapy, surgery and radiotherapy. Gene therapy for these tumours is theref ore a very attractive therapeutic modality which due to the severity of the disease is already in clinical trials. On the other hand, pituitary tumour s are usually benign, and in most cases, treatment is successful. Neverthel ess, there are some instances, especially with the macroadenomas and some i nvasive tumours in which treatment fails. Gene therapy strategies for these adenomas therefore needs to progress substantially in terms of safety, adv erse side effects and physiological impact on the normal pituitary gland be fore clinical implementation. In this paper, we will review gene delivery systems both viral and non-vira l and several therapeutic strategies which could be implemented for the tre atment of these diseases. These include cytotoxic approaches both condition al and direct, immune-stimulatory strategies, anti-angiogenic strategies an d approaches which harness pro-apoptotic and tumour suppressor gene targets . We will also review the models which are currently available in which the se gene therapy strategies can be tested experimentally. This new therapeutic modality holds enormous promise, but we still need sub stantial improvements both from the delivery, efficacy and safety stand poi nts before it can become a clinical reality.