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. 2021 Mar 19;4(1):1–16. doi: 10.20517/cdr.2020.61

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