Antisense Oligonucleotides Therapy in the Treatment of Cerebral Gliomas: A Review

Abstract

Patients affected by cerebral gliomas, despite classical strategies adopted, show a very poor prognosis. Current treatment consists of regimens that include surgical debulking, radiation therapy, and systemic chemotherapy. However, the median survival after surgery and radiation therapy alone is 9 months, and systemic chemotherapy is minimally effective. Advances in molecular biology have better depicted the mechanisms involved in the genesis of cerebral gliomas and identified specific gene sequences to be targeted in the malignant cell genome. Gene expression can be blocked using various strategies. The concept of antisense-mediated gene inhibition has now emerged as a potentially powerful alternative or adjunct to conventional cancer chemotherapy. This strategy is able to block selectively glioma cells which interfer to gliomagenesis molecular pathways. The antisense molecules, delivered inside the brain, penetrate into glioma cells blocking specific genic functions. Antisense oligonucleotides are complementary to the target mRNA and this bind cause the block and/or the reduction of the encoded protein synthesis. Genes coding for growth factors and their receptors, proto-oncogenes, cellular proteases, kinases, and proteins important in cell cycle control and apoptosis represent ideal target for antisense oligonucleotides treatment. In this study, we report the most relevant findings of antisense oligonucleotides application in gliomas treatment.