Table 1.
SLC transporters involved in anticancer drug delivery, their expression in normal tissues and cancers.
| Gene Name | Protein Name | Natural Substrates | Anticancer Drug Substrates |
Tissue Expression | Expression in Cancer Compared to Normal Tissues * |
References |
|---|---|---|---|---|---|---|
| SLC2A2 | GLUT2 | Glucose, glucosamine | Streptozotocin | Liver, pancreatic beta-cells, intestinal and renal epithelial cells | High expression: hepatocellular carcinoma c, invasive ductal carcinoma c, invasive colon tubular carcinoma c, pancreatic adenocarcinoma c, lung mesothelioma c, | [28,29,30,31,32] |
| SLC7A5 | LAT1 | Phenylalanine, leucine, tryptophan | Melphalan, acivicin | Brain (endothelial cells), testis, retina, esophagus, testis, placenta and bone marrow | High expression: colorectal cancer a, gliomablastoma b, triple-negative breast cancer and HER2-positive breast cancers and MYC driver ER-positive breast cancer c,d | [33,34,35,36,37,38,39,40,41,42,43] |
| SLC19A1 | RFC1 | Reduced folates, antifolates | Methotrexate, pemetrexed | Ubiquitous | High expression: non-small cell lung carcinoma and squamous cell carcinoma c, MYCN- amplified neuroblastoma, colorectal carcinoma d, urothelial bladder carcinomas d Low expression: ovarian cancers c |
[44,45,46,47,48,49,50,51,52,53] |
| SLCO1A2 | OATP1A2 | Bile salts, organic anions and cations | Imatinib, methotrexate | Brain (endothelial cells), kidney, intestine, liver, eye | High expression: breast cancer, glioblastoma c
Low expression: colorectal carcinoma liver metastases a, colorectal carcinoma d, |
[35,54,55,56,57,58,59] |
| SLCO1B1 | OATP1B1 | Bile salts, organic anions | Cisplatin, carboplatin, Oxaliplatin, regorafenib, belzutifan, SN-38, etoposide, tamoxifen, sorafenib | Liver | High expression: ovarian d, colon d and pancreaticc cancers, castration resistant prostate cancer metastases d Low expression: hepatocellular carcinoma a, low in colorectal carcinoma liver metastases a, |
[35,54,55,60,61,62,63] |
| SLCO1B3 | OATP1B3 | Bile salts, organic anions | Nilotinib, belzutifan, docetaxel, SN-38, oxaliplatin, carboplatin, cisplatin, imatinib, gefitinib, sorafenib, belzutifan | Liver | High expression: breast cancer c,d, colorectal carcinoma c,d, castration resistant prostate cancer metastases d
Low expression: hepatocellular carcinomaa, colorectal carcinoma liver metastases a |
[35,55,60,63] |
| SLCO2B1 | OATP2B1 | E-3-S, DHEAS | Etoposide, erlotinib | Liver, placenta, intestine, eye | High expression: prostate cancer with high Gleason score d and castration resistant prostate cancer metastases d
Low expression: hepatocellular carcinoma a, low in colorectal carcinoma liver metastases a |
[35,63,64] |
| SLCO4C1 | OATP4C1 | L-homoarginine | Methotrexate | Kidney | High expression: castration resistant prostate cancer metastases d | [35,63] |
| SLC22A1 | OCT1 | Organic cations | Dasatanib, nintendanib | Liver, small intestine, kidney, lung, heart, skeletal muscle, brain (endothelial cells, neurons), adipose tissue, immune cells | Low expression: hepatocellular carcinoma a, colorectal carcinoma liver metastases a, cholangiocellular carcinoma c,d | [60,65,66,67,68,69,70] |
| SLC22A2 | OCT2 | Organic cations | Cisplatin, oxaliplatin | Kidney, small intestine, trachea and bronchi placenta, thymus, brain (neurons, endothelial cells), inner ear | High expression: clear cell renal carcinoma c,d
Low expression: hepatocellular carcinoma c |
[65,67,68,70,71,72,73,74,75] |
| SLC22A3 | OCT3 | Organic cations | Oxaliplatin | Heart, skeletal muscle, brain (neurons, glial cells, choroid plexus), small intestine, liver, lung, kidney, urinary bladder, mammary gland, skin blood vessels | High expression: head and neck squamous cell carcinoma c, colorectal carcinoma c Low expression: colorectal carcinoma liver metastases a, hepatocellular carcinoma c, cholangiocellular carcinoma c,d |
[55,65,68,69,76,77,78,79,80,81,82,83,84] |
| SLC22A4 | OCTN1 | Ergothioneine, zwitterions, organic cations | Doxorubicin, mitoxantrone, imatinib, cytarabine | Kidney, intestine, spleen, heart, skeletal muscle, brain, mammary gland, thymus, prostate, airways, testis, eye, foetal liver, sperm, immune cells | Not found | [66,85,86,87,88,89,90] |
| SLC22A5 | OCTN2 | Zwitterions (L-carnitine), organic cations | Etoposide, imatinib | Skeletal muscle, kidney, prostate, lung, pancreas, heart, small intestine, adrenal gland, thyroid gland, liver | High expression: ER-positive breast cancers d, glioma | [66,91,92,93,94,95,96] |
| SLC22A6 | OAT1 | Organic anions | Methotrexate, bleomycin | Kidney, placenta, choroid plexus | Low expression: kidney renal clear cell carcinoma and kidney renal papillary cell carcinoma d | [97,98,99,100,101,102] |
| SLC22A7 | OAT2 | Organic anions | Irinotecan, docetaxel, 5-fluorouracil | Liver, kidney, eye | Low expression: colorectal carcinoma liver metastases a, kidney renal clear cell carcinoma and kidney renal papillary cell carcinoma d | [55,97,102,103,104,105,106,107] |
| SLC22A8 | OAT3 | Organic anions | Methotrexate | Kidney, choroid plexus | Low expression: kidney renal clear cell carcinoma and kidney renal papillary cell carcinoma d | [97,98,99,100,101,102] |
| SLC28A1 | CNT1 | Pyrimidine nucleosides and adenosine | Gemcitabine | Kidney, liver, small intestine, bone marrow macrophages and the brain | High expression: serous, mucinous and endometroid ovarian carcinomas c, uterine cervix carcinomas c
Low expression: clear cell ovarian carcinomas c, pancreatic ductal adenocarcinoma d |
[108,109,110,111,112,113,114,115] |
| SLC28A2 | CNT2 | Purine nucleosides and uridine | Gemcitabine,5-fluorouridine, 5-fluoro-2′-deoxyuridine | Heart, skeletal muscle, liver, kidney, intestine, pancreas, placenta, brain, spleen, rectum, colon, immune system | High expression: lung, ovary, uterus and prostate cancers d
Low expression: hepatocellular carcinoma, colorectal carcinoma, colorectal carcinoma liver metastases d, kidney, stomach, rectum and small intestine cancers d |
[110,113,116,117,118,119,120,121] |
| SLC29A1 | ENT1 | Nucleosides, nucleobases, creatinine, guanidine, thiamine | Gemcitabine, cytarabine, 5-fluorouracil, 6-mercaptopurine | Ubiquitous | High expression: ovarian, endometrial and uterine cervix carcinomas c
Low expression: pancreatic ductal adenocarcinoma d, prostate cancer d |
[35,113,114,115,122,123,124,125] |
| SLC29A2 | ENT2 | Nucleosides, creatinine, thiamine, carnitine | 5-fluorouracil, gemcitabine | Ubiquitous | High expression: mantle-cell lymphoma d, hepatocellular carcinoma d, ovarian, endometrial and uterine cervix carcinomas c | [35,113,114,122,123,124,125,126,127] |
| SLC31A1 | CTR1 | Copper (I) | Cisplatin, carboplatin, oxaliplatin | Liver, lung | High expression: bladder cancer c | [128,129,130,131,132] |
| SLC46A1 | PCFT | Reduced folates, folic acid | Pemetrexed | Small intestine, choroid plexus, kidney, liver, placenta, retinal pigment epithelium | High expression: colorectal cancer d, ER-positive breast cancer d | [51,133,134,135,136,137,138,139,140,141] |
| SLC47A1 | MATE1 | TEA, MPP | Oxaliplatin | Liver, kidney, muscle | Low expression: KRAS-driven colorectal carcinoma c | [142,143,144,145,146] |
| SLC47A2 | MATE2 | TEA, MPP | Oxaliplatin | Kidney | Not found | [143,146,147,148] |
* The information includes only reports in which transporter expression was compared between healthy and cancer tissue and differences were detected, a protein expression measured by quantitative targeted absolute proteomics, b protein expression measured by western blot, c semiquantitative immunohistochemistry, d mRNA expression.