Table 4.
Resistance mechanisms mediated by GLI in various tumors.
| Tumor Type | Resistant to: | Resistance Mechanism | Reference |
|---|---|---|---|
| Lung cancer | Staurosporine | GLI1-mediated upregulation of NDRG1 and downregulation of c-MYC and N-MYC | [276] |
| Gefitinib | Upregulation of SHH, SMO and GLI1 (reversible by sulforaphane) | [277] | |
| Platinum and gefitinib/erlotinib | MEOX-2-dependent GLI1 upregulation | [278] | |
| Platinum | Hedgehog pathway activation | [279] | |
| EGFR inhibitors | GLI1-mediated upregulation of SOX2, induction of EMT | [105,280] | |
| Lung and colorectal cancer | Topoisomerase inhibitors | GLI1-mediated upregulation of BID | [281] |
| Colorectal cancer | 5-Fluorouracil | Upregulation of GLI1 and GLI2 and their targets | [282] |
| Vorinostat | GLI1-mediated upregulation of BCL2L1 | [283] | |
| Gastrointestinal cancer | 5-Fluorouracil, cisplatin | GLI2-mediated upregulation of ABCG2 transporter | [284,285] |
| Doxorubicin | GLI2-mediated upregulation of ABCG2 transporter | [286] | |
| Imatinib | GLI-mediated upregulation of KIT | [287] | |
| Esophageal cancer | Chemoradiation | Nuclear localization of GLI1 | [288] |
| Hepatocellular cancer | Sorafenib | GLI2-mediated upregulation of ABCC1 transporter | [289] |
| Glioblastoma | Temozolomide | GLI1-mediated upregulation of MGMT | [290,291] |
| Clear cell renal carcinoma | Sunitinib | GLI2 overexpression | [292] |
| Ovarian cancer | Cisplatin | Rab23-mediated upregulation of ABCG2 through GLI1 | [293,294] |
| Basal cell carcinoma | Gdc-619 | SRF-mediated upregulation of GLI1 | [295] |
| Head and neck squamous cancer | Radioresistance | mTOR/SK6-mediated upregulation of GLI1 | [296] |
| Multiple myeloma | Lenalidomide | ADAR1-dependent RNA editing of GLI1 | [144] |
| Bortezomib | Downregulation of mir-324-5p leading to upregulation of SMO and GLI1 | [297] | |
| Chronic myeloid leukemia | Imatinib | GLI1-mediated upregulation of BCR-ABL, p-Akt, Bcl-xl and survivin (reversible by oroxyloside A) | [298] |
| Acute myeloid leukemia | Radiation | Activation of the GLI1/PI3K/AKT/NFKB pathway | [299] |
| Ribavirin/cytarabine | GLI1-mediated upregulation of UDP-glucuronosyl transferase enzymes | [300] |