EXTH-34. ANTI-RETROVIRAL REPURPOSING FOR TREATMENT OF GLIOBLASTOMA

Abstract Glioblastoma (GBM) is a WHO grade IV glioma whose heterogeneous nature and stem-like features contribute to resistance conventional chemotherapeutics. Previously, antiretrovirals have been proposed as anti-neoplastic agents, but their clinical efficacy limited. With the advent of modern anti-retroviral combinatorial therapy, we sought repurpose FDA-approved drugs for glioblastoma. Here, performed an unbiased screen 16 in 40 cell lines using DEPMap drug repositioning. We identified six potential among several classes with significant anti-glioma activity: abacavir (ABC), lamivudine (LMV), raltegravir (RLT), darunavir (DAR), indinavir (IND), etravirine (ETV). validated effects on patient-derived GBM neurospheres (GBM28 GBM43) established line (A172). The non-nucleoside reverse transcriptase inhibitor (ETV) had lowest effective IC50 chemoresistant PDX (15uM) A172 cells (2.7uM). Synergy assessment ETV standard care temozolomide (TMZ) demonstrated that these work independently one another (Bliss score -0.39 -0.83 28 43, respectively). In addition, investigated effect stemness human endogenous retroviral elements. Western blot, immunofluorescence qPCR showed decrease markers, OCT-4, HERV-K env expression. Reverse levels decreased significantly after sublethal treatment (5uM) 48 hours GBMNS not adherent cells. Overall, antiretroviral could be repositioned glioblastoma therapy. Given its ideal therapeutic index ability penetrate blood-brain barrier, may promising candidate future trials neuro-oncology.