Antisense Strategies in Therapy of Gliomas

Jerzy      Trojan; Donald      D. Anthony

doi:10.2174/157436211797483895

Abstract

The malignant brain tumour, glioblastoma, is invariably fatal with an average survival of 8-11 months (recent pharmacology has increased the median survival to 15, and rarely to 18 months). Different growth factors participate in the malignant development of the brain, especially IGF-1, EGF, TGF-beta and VEGF. Among the strategies applied to target and arrest the expression of growth factors, their receptors (tyrosine kinase) and down stream signalling pathway elements (i.e. PKC, Bcl-2, glycogen synthase) involved in cancer processes, the use of different inhibitors and especially of antisense technique has been among the leading technology proposed.

Recent clinical results of glioblastomas are especially promising in situations in which antisense was used either as gene therapy (antisense anti TGF beta oligodeoxynucleotides), or as cellular gene therapy (transfection with antisense anti IGFI expression vector), following a classical surgery, radio- and chemotherapy. Using anti - IGF-I approach, median survival in glioblastoma patients has reached 21 months. The immune anti-tumour response in treated patients was confirmed by an increase of CD8+ T level in peripheral blood lymphocytes.

Keywords: antisense nucleotides, growth factors and signal transduction, gene and cellular therapies, gliomas, glioblastoma, gene therapy, cellular therapy, antisense, antisense RNA, triple helix, IGF-I, IGF-I expression vector, IGF-I receptor, EGF, VEGF, TGFbeta, tyrosine kinase, PKC, bcl2, glycogene synthase, apoptosis, CD8, CD28, MHC-I, B7, APC, median overall survival