A new aptamer for glioblastoma diagnosis and treatment

Glioblastoma Multiforme (GBM) is the most aggressive human brain tumor, with an overall median survival of ۱۳.۵ months. Despite intensive treatment, GBM often shows chemo- and radiotherapy resistance, which inevitably result in tumor relapse. A growing body of evidence shows that a sub-population of Glioblastoma Stem Cells (GSCs) may play a pivotal role in GBM tumorigenesis, as well as in therapeutic resistance and relapse. A potential strategy to improve the outcome of GBM patients could be the selective inhibition and eradication of GSCs, which can result in sensitization to therapy and tumor regression. Here, we characterized the functional activity of the RNA aptamer ۴۰L and its truncated form A۴۰s, which selectively bind GSCs. We demonstrated that ۴۰L and A۴۰s can inhibit proliferation, migration, and self-renewal and promote differentiation of GSCs by targeting the receptor tyrosine kinase EphA۲, an innovative potential marker of GSCs. Also, we demonstrated that A۴۰s can bind EphA۲-carrying exosomes from GBM cells in culture and from the serum of GBM patients. The results of our work open the possibility to use ۴۰L and A۴۰s as targeted therapeutic agents for GBM through the selective inhibition and eradication of GSCs, as well as a diagnostic tool for the detection of GBM-derived circulating exosomes.