Challenges to overcome | Prospective solutions | Novelty | Representative study |
1. Heterogeneity and invasive properties of GBM | Stem cell (SC) carriers |
| 89 90 |
Adjuvant viral therapy |
| 91 | |
Nanoparticles | Offer precise interference and silencing of novel genes. | 87 | |
Next generation OV vectors |
| 59 | |
2. Anatomical and physiological features of central nervous system and GBM | SC carriers | Increase spatial distribution of gene therapeutics. | 83 |
Nanoparticles | Ability to cross BBB permits systemic administration. | 92 | |
Convection-enhanced delivery |
| 93 | |
Next generation OV vectors | Increased vector penetration and transduction efficiency. | 62 | |
3. Host immune system | Genetic immunotherapy and vaccination |
| 78 79 |
SC carriers | Mask gene therapy vectors from host immune system clearance. | 94 | |
4. Inadequacy of preclinical models | Advanced imaging protocols |
| 95 |
Superior animal models |
| 96 |
BBB, blood–brain barrier; GBM, glioblastoma multiforme; GSC, glioma stem cell; IL-4, interleukin 4; OV, oncolytic virus; TNFα, tumour necrosis factor α; VEGF, vascular endothelial growth factor; shRNA, short hairpin RNA.