Applications of organoids in GBM research
| Application | Targets | Mechanisms | References |
|---|---|---|---|
| Biological function study | Inflammation | Dendritic polyglycerol sulfate limits GBM invasiveness by modulating microglial activation in GBOs. | 45 |
| Lipid metabolism | GSCs have lower lipid droplet accumulation than non-GSCs in GBO models and xenograft tumors. | 46 | |
| Invasion | lncGRS antisense nucleotides decrease aggressive growth of tumors in GBOs. | 47 | |
| Proliferation | EGFRvIII mutation-induced astrogenesis and massive cell proliferation in human GBOs are observed. | 48 | |
| Microenvironment | Quiescent cells are partially responsible for tumor cell infiltration and invasion in GBOs. | 49,50 | |
| Drug treatment | Gamitrinib | Gamitrinib inhibits cell proliferation, and induces cell apoptosis and death, in 17 primary glioma cell lines, 6 TMZ-resistant glioma cell lines, 4 neurospheres, and 3 PDOs. | 56 |
| UM-002 | The novel BET inhibitor UM-002 decreases glioblastoma cell proliferation and invasion in GBOs. | 57 | |
| Atorvastatin | Atorvastatin has potent anti-angiogenic and apoptosis inducing effects against glioma spheroids. | 58 | |
| Temozolomide | Bioprinted GBOs reproduce clinically observed patient-specific resistance to treatment with concurrent chemoradiation and temozolomide. | 38 | |
| Ruxolitinib | Patients with GBM with than without LPS expression have higher levels of STAT1 and STAT2, and are more sensitive to ruxolitinib therapy. | 59 | |
| Luteolin | Luteolin decreases the proliferation of patient-derived glioma initiating cells and tumor organoids, but does not affect normal astrocytes. | 60 | |
| Costunolide | The TERT inhibitor costunolide effectively decreases cell viability in both primary GBO models and GBO models pre-treated with chemotherapy and radiotherapy. | 61 | |
| MON | MON decreases U87MG tumor size in GBOs and significantly decreases PARP expression. | 62 | |
| GSC research | PTEN | GSCs are highly sensitive to proteasome inhibition, owing to an increased protein synthesis rate and loss of autophagy, associated with PTEN loss and activation of the PI3K/mTOR pathway. | 68 |
| Ciliogenesis | Ciliogenesis-induced differentiation prevents the infiltration of GSCs in GBOs. | 69 | |
| Phenotype | Different microenvironments produced by transfer of GSC clonal populations from adherent culture to organoid conditions have different clonal phenotypes and are highly plasticized. | 70 | |
| ZIKV | ZIKV selectively eliminates GSCs from species-matched human mature cerebral organoids and GBM surgical specimens, but this effect is reversed by integrin αvβ5 inhibition. | 71 | |
| ICB therapy | HSPA7 promotes macrophage infiltration and SPP1 expression via upregulating YAP1 and LOX expression in GSCs. Knockdown of HSPA7 increases the efficiency of anti-PD1 therapy in the GBO model. | 72 |