Table 1.
Summary of studies describing EV-mediated mechanisms of EV resistance in GBM
| Author, year | Therapy | Mechanism of EV mediated resistance transfer | Genetic cargo evaluated | Functional implication | Validation: in vitro/in vivo |
|---|---|---|---|---|---|
| Zhang et al.[111], 2019 | TMZ | EV mediated cargo transfer | lncRNA, lncSBF2-AS | Enhanced DNA damage repair by upregulating lncSBF2-AS1-miR-151a-3p-XRCC4 DNA repair axis | Both |
| Yin et al.[112], 2019 | TMZ | EV mediated cargo transfer | miRNA, miR-1238 | Anti-apoptotic function by the activation of EGFR-PI3K-Akt-mTOR pathway | Both |
| Chuang et al.[121], 2019 | TMZ | GBM associated macrophage EV mediated cargo transfer | miRNA, miR-21-5p | Enhanced survival by modulating tumor suppressor gene, PDCD4 and enhancing STAT3/JAK 2 pathway | Both |
| Zeng et al.[104], 2017 | TMZ | EV mediated cargo transfer from (PTPRZ1-MET-ZM fusion positive cells) | Specific cargo not identified | - | Both |
| Munoz et al.[114], 2019 | TMZ | EV mediated cargo transfer | miRNAs, miR-93, miR-193 | Decrease cell cycling quiescence by targeting Cyclin D1 | In vitro |
| Yu et al.[109], 2018 | TMZ | GBM associated Astrocyte EV mediated cargo transfer | mRNA, MGMT | Transfer of MGMT mRNA increases DNA repair enzymes in recipient cells | Both |
| Shao et al.[110], 2015 | TMZ | EV mediated cargo transfer | mRNA, MGMT and APNG | Transfer of MGMT, APNG mRNA increases DNA repair enzymes in recipient cells | In vitro |
| Pavlyukov et al.[105], 2018 | Radiation, TMZ, Cisplatin | EV (Apoptotic) mediated cargo transfer | Spliceosome, RBM11 | RBM11 switches splicing of MDM4 and Cyclin D1 | Both |
| André-Grégoire et al.[108], 2018 | TMZ | EV mediated cargo transfer | Proteolytic and mRNA processing proteins, adhesion related proteins | - | In vitro |
| Mrowczynski et al.[113], 2018 | Radiation | EV mediated cargo transfer | Upregulated: miRNA, miR-889 mRNA, WWC1
Downregulated: miRNA, miR-365 |
Upregulated miR-889 (inhibits DAB2IP expression), mRNA WWC1, and downregulated miR-365 (disinhibiting expression of Cyclin-D1, BCL-2, and PI3K and PTEN) increases radioresistance | Both |
| Zhang et al.[102], 2020 | Radiation | GBM associated macrophage EV mediated cargo transfer | miRNAs, miR-27a-3p, miR-22-3p and miR-221-3p | Promoted proneural to mesenchymal transition by targeting CHD7 pathway | Both |
| Yue et al.[103], 2019 | Radiation | Hypoxia induced EV mediated cargo transfer | miRNA, miR-301a | Activates Wnt/β-catenin Signalling and inhibiting TCEAL7 | In vitro |
| Dai et al.[107], 2019 | Radiation | EV mediated cargo transfer from AHIF positive cells | Specific cargo not identified | AHIF-mediated p53 downregulation and anti-apoptosis | In vitro |
| Ramakrishnan et al.[106], 2020 | Radiation | miRNA export | miRNA, miR-603 | miR-603 export causes de-repression of IGF1, IGF1R and MGMT leading to radioresistance and TMZ resistance | Both |
| Simon et al.[127], 2018 | Bevacizumab | Decoys | - | Reduced bioavailability of bevacizumab | In vitro |
AHIF: antisense transcript of hypoxia-inducible factor-1α; APNG: alkyl purine-DNA-N-glycosylase; EV: extracellular vesicles; GBM: glioblastoma; IGF1: insulin-like growth factor 1; IGF1R: insulin-like growth factor 1 receptor; MGMT: O(6)-methylguanine-DNA methyltransferase; TMZ: temozolomide