Table 2 Summary of drugs targeting the sonic hedgehog signalling pathway in central nervous system tumours
From: Sonic hedgehog signalling pathway in CNS tumours: its role and therapeutic implications
Therapeutic agents | Examples and functions |
|---|---|
1. SMO inhibitors [130, 132,133,134, 136,137,138, 142,143,144,145,146,147] | GDC-0449 (Vismodegib): Inhibits SHH pathway, showing potential in treating metastatic MB HhAntag: Complements GDC-0449 by blocking SMO through additional binding sites Cyclopamine: Reduces growth rates of gliomas, GBMs, and MBs, enhances TMZ therapy by inducing apoptosis LDE-225 (Sonidegib): Induces cell cycle arrest and apoptosis, reduces epithelial-mesenchymal transition in multiple cancers IPI-926 (Saridegib): Suppresses tumour growth in MB allograft models BMS-833923: Decreases GLI1 and PTCH1 mRNA expression, inhibiting proliferation PF-5274857: Selective SMO antagonist, effective in MB allograft models TAK-441: Effective against Vismodegib-resistant SMO mutants LY2940680 (Taladegib): Inhibits HH signalling, effective against Vismodegib-resistant SMO mutants. Itraconazole: Inhibits SMO accumulation, effective in MB allograft models, synergistic with cyclopamine |
2. GLI inhibitors [148] | GANT 61: Inhibits DNA binding of GLI1 and GLI2, downregulates GLI1, c-MYC, MYCN, Cyclin D1, induces apoptosis in NB cells, enhances effects of chemotherapeutic drugs |
3. SHH inhibitors [153] | Target multiple components of the SHH signalling cascade, showing effectiveness in the breakdown of GBM cancer stem cells, preventing tumour recurrence - 5E1: Monoclonal antibody targeting SHH ligand, inhibits MB growth, reduces tumour proliferation, increases apoptosis, improves survival rates |
4. DNA methyltransferase inhibitors [155] | Restore epigenetically silenced SHH pathway inhibitors, such as PTCH1, HHIP, and SFRP1, suggesting potential therapeutic approach for modulating SHH signalling in NBs |