Table 5.
Mechanisms of chemoresistance type 5 (MOC-5) in colorectal cancer.
| Protein | Change | Drugs Affected | Consequences | References |
|---|---|---|---|---|
| Pro-Apoptotic Factors (MOC-5a) | ||||
| BAD | Downregulation | 5-FU | Apoptosis inhibition | [162] |
| BAX | Downregulation and inactivating mutations | 5-FU | Apoptosis inhibition | [159,160] |
| BID | Downregulation | 5-FU | Apoptosis inhibition | [162] |
| FADD | Downregulation | 5-FU | Apoptosis inhibition | [163] |
| miR-520g | Upregulation | 5-FU, Oxaliplatin | No cell cycle arrest; apoptosis inhibition; p21 downregulation | [158] |
| p53 | Inactivating mutations | 5-FU, FOLFOX | No cell cycle arrest; apoptosis inhibition | [149,150,155,156] |
| Oxaliplatin | miR-503-5p upregulation; PUMA downregulation; apoptosis inhibition | [151,152] | ||
| 5-FU | Associated with enhanced MDR1 and GSTP expression | [153,154] | ||
| Survival Pathways (MOC-5b) | ||||
| APC | Inactivating mutations | 5-FU | Stimulation of Wnt/β-catenin | [180] |
| BCL-2 | Upregulation | 5-FU | Apoptosis inhibition | [166,167] |
| Biglycan | Upregulation | 5-FU | Increased activity of the NFκB pathway | [178] |
| BRAF | Inactivating mutations | Vemurafenib, Dabrafenib, Encorafenib | Increased proliferation | [181,182] |
| CD133 | Upregulation | Doxorubicin | Increased activity of the NFκB pathway; MDR1 upregulation | [179] |
| CHK1 | Upregulation | 5-FU, Oxaliplatin | No cell cycle arrest; apoptosis inhibition | [173,174] |
| IAP2 | Modulation of caspase 3/7 activity | 5-FU | Apoptosis inhibition | [171] |
| IL-17 | Upregulation of p-AKT, mTOR and BCL-2; Suppression of BAX | Cisplatin | Apoptosis inhibition | [164] |
| KRAS | Activating mutations | Cetuximab, Panitumumab, others | Increased proliferation | [148,183,184] |
| MCL-1 | Perinuclear expression | 5-FU | No cell cycle arrest; apoptosis inhibition | [172] |
| NFκB | Increased activity | 5-FU, Gemcitabine | Upregulation of anti-apoptotic factors | [175,176,177] |
| Notch | Increased activity | 5-FU, Cisplatin | Upregulation of COX2; MDR1 and MRP1 upregulation | [185,186] |
| RNF43 | Inactivating mutations | Dacomitinib | Stimulation of Wnt/β-catenin | [187] |
| Wnt/β-catenin | Increased activity | 5-FU | Stimulation of cell proliferation | [188] |
| ZNRF3 | Inactivating mutations | Dacomitinib | Stimulation of Wnt/β-catenin | [187] |
5-FU: 5-fluorouracil; FOLFOX: oxaliplatin/leucovorin (folinic acid)/5-FU regimen.