Table 4.
Molecular events of ULK1-related cancer drug resistance.
| Drug Resistance Cancer Cell Type | Event | Effects on Cancer Drug Resistance |
|---|---|---|
| Chronic myeloid leukemia (CML) resistance to tyrosine kinase inhibitors | A mutation in the BCR-ABL protein; IIB02 producing significant cytotoxicity to BCR-ABL mutation cells BIIB021 inducing autophagic cell death by the downregulation of AKT-mTOR pathway and the activation of ULK1 | Overcoming drug resistance |
| Colorectal cancer (CRC) resistance to selective BRAF inhibitors | A mutation in BRAF protein; BRAFV600E of colorectal cancer (CRC) develops drug resistance to selective BRAF inhibitors is that BRAF inhibitors induce cytoprotective autophagy through AMPK-ULK1 pathway | Inhibiting autophagy and overcoming drug resistance |
| Colorectal cancer cell resistance to 5-fluorouracil (5-FU) | SNHG6 enhances chemoresistance through ULK1-induced autophagy via reducing free miR-26a-5p | Inhibiting autophagy, SNHG6 knockdown or overexpression of miR-26a-5p, thus overcoming drug resistance |
| Colon cancers resistance to KRAS drugs | Two mitochondrial targeted compound 3-Carboxyl proxyl nitroxide (Mito-CP) and Mito-Metformin cause mitochondrial autophagy of KRAS cells by activating AMPK-ULK1 signaling cascade | Overcoming drug resistance of KRAS mutant cells |
| Non-small cell lung cancer (NSCLC) cells resistance to NK cell-mediated killing | The natural product rocaglamide (RocA) inhibited autophagy by targeting to ULK1 and restored the level of NK cell-derived GZMB (granzyme B) in NSCLC cells increasing their susceptibility to NK cell-mediated killing. | Overcoming resistance of NSCLC cells against NK cell-mediated killing |
| Breast cancer cell resistance to doxorubicin (DOX), tamoxifen and cisplatin | Mir-489 directly targeting ULK1 and LAPTM4B genes, negatively regulating the expression of ULK1 and LAPTM4B inhibiting autophagy | Overcoming resistance to doxorubicin (DOX), tamoxifen and cisplatin |
| NSCLC resistance to crizotinib | HOTAIR (HOX transcript antisense intergenic RNA) is a high expression in NSCLC and promotes cisplatin resistance in NSCLC | HOTAIR shRNA transfection overcoming the resistance of A549 cells to crizotinib by inhibiting autophagy activity decreasing the phosphorylation of ULK1 |
| Cisplatin-resistant NSCLC cells | SBI0206965, as a selective inhibitor of ULK1 blocks cisplatin-induced autophagy and promotes cell death | Overcoming NSCLC cells resistance to cisplatin |