RNA-based precision medicine in glioblastoma driven by oncogenic gene fusions

Glioblastoma, the most common primary central nervous system tumor, is the leading cause of death in neuro-oncology. Gene fusions, caused by chromosomal rearrangements, may act as drivers of tumorigenesis in glioblastoma. These fusions result from the juxtaposition of two genes, leading to the production of a chimeric protein and, in most cases, constitutive activation of a tyrosine kinase receptor. Despite the use of tyrosine kinase inhibitors to block the oncogenic activity of gene fusions, clinical responses in glioblastoma remain poor compared to those in other cancers, highlighting the need for innovative therapeutic strategies. RNA interference, using small interfering RNAs or micro-RNAs, offers a promising approach to target these oncogenic fusions. Through specific silencing, small interfering RNAs spare healthy cells, avoiding the adverse effects associated with tyrosine kinase inhibitors. Recent advances in biotechnology (e.g., antisense oligonucleotides and aptamers) and delivery systems have improved small interfering RNA stability, specificity, and ability to cross the blood-brain barrier. This review discusses these advances and their potential applications to target oncogenic gene fusions in glioblastoma. RNA interference-based therapy represents a critical area of research that could improve the survival of patients with glioblastoma.