Table 1.
Mechanisms of chemoresistance type 1 (MOC-1) in colorectal cancer.
| Protein | Change | Drugs Affected | Consequences | References |
|---|---|---|---|---|
| Uptake Transporters (MOC-1a) | ||||
| OATP1B1 | GV (OATP1B1*15 haplotype) | Irinotecan, Methotrexate | Lower response in vitro and in patients | [11,15,16,18,19] |
| OATP1B3 | GV (Cancer-type) | Irinotecan | Reduced PFS | [21,22,23] |
| OATP1A2 | Downregulation | Imatinib, Methotrexate | Reduced drug uptake | [16,27] |
| OCT1 | Downregulation | Imatinib, Doxorubicin | Lower sensitivity in vitro; lower clinical response | [32,33,34,35] |
| OCT3 | Impaired expression | Irinotecan, Imatinib, Cisplatin, 5-FU, FOLFOX | Lower clinical response | [38,39] |
| OCTN2 | GV (rs2631367, rs2631372) | Imatinib, Etoposide | Lower sensitivity in vitro | [38,42,43,44] |
| CTR1 | Downregulation | Cisplatin | Lower sensitivity in vitro | [60] |
| Efflux transporters (MOC-1b) | ||||
| MDR1 | Upregulation | Doxorubicin, Etoposide, Irinotecan | Lower sensitivity in vitro | [47] |
| MRP1 | Upregulation | Doxorubicin, Etoposide, 5-FU, Oxaliplatin | Lower sensitivity in vitro | [61,62] |
| MRP2 | Upregulation | Cisplatin | Lower sensitivity in vitro | [56] |
| MRP3 | Upregulation | Doxorubicin, Etoposide | Lower sensitivity in vitro | [63] |
| MRP4 | GV (rs3742106) | 5-FU, Capecitabine | Lower clinical response | [64] |
| MRP5 | Upregulation | 5-FU, Methotrexate | Lower sensitivity in vitro | [65] |
| BCRP | GV (rs2231137, rs2231142) | Irinotecan | Lower sensitivity in vitro; Lower clinical response | [66,67] |
| ATP7B | Upregulation | Oxaliplatin | Poor clinical outcome | [68] |
| ABCA9 | GV | Oxaliplatin | Reduced OS and response | [69] |
| LRP | Upregulation | Doxorubicin, Etoposide | Lower sensitivity in vitro | [70,71] |
5-FU: 5-fluorouracil; FOLFOX: leucovorin (folinic acid), 5-FU, and oxaliplatin regimen; GV: genetic variant; OS: overall survival; PFS: progression-free survival.