Table 1.
Overview of clinical trials showing selected chemotherapeutics, indication, and association between single nucleotide polymorphisms (SNPs) of SLC transporters and therapy response.
| Chemotherapeutic Alone or in Combination (Administration) | Tumor Indication | Transporter | SNP | Response to Treatment (Defined Criteria) | Study Design and Patient Number |
|---|---|---|---|---|---|
| Abiraterone (p.o.) | Prostate cancer | OATP2B1 | rs12422149 rs1789693 |
Higher mean drug tissue levels Lower mean drug tissue levels |
Clinical trial, 58 patients [40] |
| Prostate cancer | OATP2B1 | rs12422149 | Improved progression-free survival (less increase in PSA and/or radiographic or clinical progression) | Retrospective, 79 patients [41] | |
| Cisplatin (i.v.) | Different malignant solid tumors | OCT2 | rs316019 | Attenuated nephrotoxicity | Retrospective, 123 patients [42] |
| Imatinib (i.v.) | GIST | OATP1A2 | rs11568563, c.516A>C, p.E172D, OATP1A2*3 | No significant changes in imatinib plasma levels | Retrospective, 94 patients [43] |
| CML | OCT1, OCTN1, OATP1A2 | Combination of SNPs | Major (defined as a 3-log reduction in Bcr-Abl transcript level from a standardized baseline value) and complete (defined as at least a 4-log reduction corresponding to undetectable Bcr-Abl transcript by PCR) molecular response | Retrospective, 189 patients [44] | |
| CML | OATP1A2 | −361GG | Lower clearance | Retrospective, 34 patients [45] | |
| GIST | OCTN1 OCTN2 |
rs1050152 rs2631367 rs2631372 |
Improved time to progression (calculated from the start of imatinib therapy to the date of disease progression documented by a CT scan) | Retrospective, 54 patients [46] | |
| Irinotecan (i.v.) | NSCLC | OATP1B1 | 521CC, 521TC, −11187GG |
Increased exposure of metabolite SN-38 | Phase II study, 81 patients [37] |
| Metastatic colorectal cancer and advanced/metastatic pancreatic cancer | OATP1B1 OATP1B1 |
521C c.388A>G |
Increased exposure of metabolite SN-38 Longer progression-free survival (elongated time from initiation of irinotecan-based chemotherapy to the date of progression, death, last contact, or censor date) |
Retrospective, 127 patients [38] | |
| Methotrexate (p.o./i.v.) | Rheumatoid arthritis | OATP1A2 | c.550G>A, p.E184K | Delayed MTX elimination, increased MTX related toxicity | Clinical trial, 60 patients [47,48] |
| c.553G>A, p.D185N c.775A>C, p.V255I c.862G>A, p.T259P |
No association with MTX related PK or toxicity | ||||
| Sorafenib (p.o.) | Different tumors | OATP1B1 | rs2306283 rs4149056 |
Associated with diarrhea and thrombocytopenia | Retrospective, 114 patients [25] |
| Hepatocellular carcinoma | PEPT2 | rs2257212 | Prolonged progression-free survival (Hazard ratios) | Retrospective, 174 patients [34] | |
| Sunitinib (p.o.) | GIST | OCTN2 | rs2631367 + rs2631370 + rs2631372 | Longer overall survival (Hazard ratios) | Retrospective, 127 patients [49] |
| OATP1B3 | rs4149117 | Longer overall survival (Hazard ratios) | Retrospective, 127 patients [49] | ||
| Docetaxel and Doxorubicin (i.v.) | Breast cancer | OATP1A2 | rs4762699 rs2857468 |
High risk for febrile neutropenia | Clinical trial, 155 patients [50] |
| Cytarabine, Daunorubicin, Etoposide, Mitoxantrone (i.v.) | AML | OATP1B1 | rs2291075 | Association with event-free and overall survival (Hazard ratios) | Retrospective, 165 pediatric patients [51] |
AML, acute myeloid leukemia; CML, chronic myeloid leukemia; NSCLC, non-small cell lung cancer; GIST, gastrointestinal stromal tumor; MTX, methotrexate; PCR, polymerase chain reaction; PK, pharmacokinetic; SNP, single nucleotide polymorphism.