Abstract A054: Extracellular vesicles modulate glioblastoma intratumor heterogeneity and treatment resistance

Glioblastoma (GBM) is the most common primary malignant brain tumor and despite optimal treatment, long-term survival remains uncommon. GBM can be roughly divided into three different molecular subtypes, each varying in aggressiveness and treatment resistance. Interestingly, recent evidence shows plasticity between these subtypes in which the proneural (PN) glioma stem-like cells undergo transition into the more aggressive mesenchymal (MES) subtype leading to therapeutic resistance. Extracellular vesicles (EVs) are membranous structures secreted by nearly every cell and have been shown to play a key role in GBM progression by acting as multifunctional signaling complexes. Here we show that EVs derived from MES cells educate PN cells to increase stemness, cell proliferation, tumor aggressiveness, and therapeutic resistance by modulating mesenchymal transition through NF-κB activation. Our findings could potentially help to explore new treatment strategies for GBM and indicate that EVs may also play a role in the mesenchymal transition of different tumor types. Citation Format: Markus W Schweiger, Elie Tabet, Mao Li, Tian Tian, Max Zinter, Renata Fleming, Litia A Carvalho, Michael J Saad, Bakhos A Tannous. Extracellular vesicles modulate glioblastoma intratumor heterogeneity and treatment resistance [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr A054. doi:10.1158/1535-7163.TARG-19-A054