Table 1.
Use of SHH-associated medulloblastoma models for testing of targeted therapy
| GEM | Drug | Target | GEM study outcome | Status in human clinical trials |
|---|---|---|---|---|
| Ptch1+/−; p53+/−Ptch1+/−; p53−/− allografts | Cyclopamine | SMO | Tumor regression | Preclinical only |
| Ptch1+/−; p53−/− | HhAntag-691 | SMO | Tumor inhibition, prolonged survival | Preclinical only |
| Ptch1+/−; Hic1+/−allograft | IPI-926 | SMO | Tumor regression | Phase I |
| Ptch1+/−Ptch1+/−; p53−/−Ptch1+/−; Hic1+/− allografts | NVP-LDE225 | SMO | Tumor regression, regrowth | Phase I |
| Ptch1+/− allograft | GDC-0449 | SMO | Tumor regression | Phase II |
| Ptch1+/−; p53−/− allograft | Bis-amide compound 5 | SMO | Tumor regression; regression of GDC-0449 resistant tumors | Preclinical |
| Ptch1+/−; p53−/− allograft | Arsenic trioxide | GLI | Tumor inhibition | Phase II completed |
| Ptch1+/−; p53−/− allograft | Itraconazole | SMO | Tumor inhibition | Phase I in children |
| SmoA1 | Suberoylanilide hydroxamic acid | Histone deacetylase | Increased apoptosis | |
| Ptch1+/− | Valproic acid | Histone deacetylase | Combined with 5-azaC | Phase II |
| Ptch1+/− | 5-azaC | DNA methylating agent | Prevented tumors, prolonged survival when combined with VPA | |
| Picropodophyllin | IGF-1R | Not in vivo | Preclinical | |
| SmoA1 | Gamma-secretase inhibitors | NOTCH signaling | Not in vivo? | Phase II completed |
| RCAS/tv-a SHH + HGF | HGF neutralizing antibody L2G7 | HGF | Prolonged survival | Preclinical |