Beyond the obvious: targeting the SLC transportome and non-canonical drug transport mechanisms in cancer therapy

Gottesman MM, Fojo T, Bates SE (2002) Multidrug resistance in cancer: role of ATP-dependent transporters. Nat Rev Cancer 2(1):48–58. https://doi.org/10.1038/nrc706

Robey RW, Pluchino KM, Hall MD et al (2018) Revisiting the role of ABC transporters in multidrug-resistant cancer. Nat Rev Cancer. https://doi.org/10.1038/s41568-018-0005-8

Article  PubMed  PubMed Central  Google Scholar 

César-Razquin A, Snijder B, Frappier-Brinton T et al (2015) A call for systematic research on solute carriers. Cell. https://doi.org/10.1016/j.cell.2015.07.022

Article  PubMed  Google Scholar 

Lin L, Yee SW, Kim RB, Giacomini KM (2015) Slc transporters as therapeutic targets: emerging opportunities. Nat Rev Drug Discov 14:543–560

CAS  PubMed  PubMed Central  Google Scholar 

Nies AT, Damme K, Schaeffeler E, Schwab M (2012) Multidrug and toxin extrusion proteins as transporters of antimicrobial drugs. Expert Opin Drug Metab Toxicol 8:1565–1577

CAS  PubMed  Google Scholar 

De Bruyn T, Van Westen GJP, IJzerman AP et al (2013) Structure-based identification of oatp1b1/3 inhibitorss. Mol Pharmacol 83:1257–1267. https://doi.org/10.1124/mol.112.084152

Shu Y, Sheardown SA, Brown C et al (2007) Effect of genetic variation in the organic cation transporter 1 (OCT1) on metformin action. J Clin Invest 117:1422. https://doi.org/10.1172/JCI30558

Article  CAS  PubMed  PubMed Central  Google Scholar 

Burger H, Den Dekker AT, Segeletz S et al (2015) Lysosomal sequestration determines intracellular imatinib levels. Mol Pharmacol. https://doi.org/10.1124/mol.114.097451

Article  PubMed  Google Scholar 

Huang KM, Uddin ME, DiGiacomo D et al (2020) Role of SLC transporters in toxicity induced by anticancer drugs. Expert Opin Drug Metab Toxicol 16:493–506

CAS  PubMed  PubMed Central  Google Scholar 

Rives ML, Javitch JA, Wickenden AD (2017) Potentiating SLC transporter activity: emerging drug discovery opportunities. Biochem Pharmacol 135:1–11

Bhutia YD, Babu E, Prasad PD, Ganapathy V (2014) The amino acid transporter SLC6A14 in cancer and its potential use in chemotherapy. Asian J Pharm Sci 9:293–303

Google Scholar 

Shindo H, Harada-Shoji N, Ebata A et al (2021) Targeting amino acid metabolic reprogramming via L-type amino acid transporter 1 (Lat1) for endocrine-resistant breast cancer. Cancers (Basel). https://doi.org/10.3390/cancers13174375

Article  PubMed  Google Scholar 

Clemons NJ, Liu DS, Duong CP, Phillips WA (2017) Inhibiting system xC− and glutathione biosynthesis–a potential achilles’ heel in mutant-p53 cancers. Mol Cell Oncol. https://doi.org/10.1080/23723556.2017.1344757

Article  PubMed  PubMed Central  Google Scholar 

Ciarimboli G, Deuster D, Knief A et al (2010) Organic cation transporter 2 mediates cisplatin-induced oto- and nephrotoxicity and is a target for protective interventions. Am J Pathol 176:1169. https://doi.org/10.2353/ajpath.2010.090610

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhang S, Lovejoy KS, Shima JE et al (2006) Organic cation transporters are determinants of oxaliplatin cytotoxicity. Cancer Res. https://doi.org/10.1158/0008-5472.CAN-06-0769

Article  PubMed  PubMed Central  Google Scholar 

Assaraf YG (2007) Molecular basis of antifolate resistance. Cancer Metastasis Rev 26:153–181

White DL, Saunders VA, Dang P et al (2006) OCT-1-mediated influx is a key determinant of the intracellular uptake of imatinib but not nilotinib (AMN107): reduced OCT-1 activity is the cause of low in vitro sensitivity to imatinib. Blood 108:697. https://doi.org/10.1182/blood-2005-11-4687

Article  CAS  PubMed  Google Scholar 

Zimmerman EI, Hu S, Roberts JL et al (2013) Contribution of OATP1B1 and OATP1B3 to the disposition of sorafenib and sorafenib-glucuronide. Clin Cancer Res 19:1458. https://doi.org/10.1158/1078-0432.CCR-12-3306

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gloeckner-Hofmann K, Guillén-Gómez E, Schmidtgen C et al (2006) Expression of the high-affinity fluoropyrimidine-preferring nucleoside transporter hCNT1 correlates with decreased disease-free survival in breast cancer. Oncology 70:238. https://doi.org/10.1159/000094541

Article  CAS  PubMed  Google Scholar 

Sugawara M, Nakanishi T, Fei YJ et al (2000) Cloning of an amino acid transporter with functional characteristics and tissue expression pattern identical to that of system A. J Biol Chem 275:16473. https://doi.org/10.1074/jbc.C000205200

Article  CAS  PubMed  Google Scholar 

Hediger MA, Clémençon B, Burrier RE, Bruford EA (2013) The ABCs of membrane transporters in health and disease (SLC series): Introduction. Mol Aspects Med 34(2–3):95–107. https://doi.org/10.1016/j.mam.2012.12.009

Yan R, Zhao X, Lei J, Zhou Q (2019) Structure of the human LAT1–4F2hc heteromeric amino acid transporter complex. Nature 568:127. https://doi.org/10.1038/s41586-019-1011-z

Article  CAS  PubMed  Google Scholar 

Liu Y, Wu J, Li W et al (2023) Responsive metal–organic framework nanocarrier delivery system: an effective solution against bacterial infection. Coord Chem Rev 496:215431

CAS  Google Scholar 

Transporter C, Giacomini KM, Huang SM, Tweedie DJ, Benet LZ, Brouwer KL, Chu X, Dahlin A, Evers R, Fischer V, Hillgren KM (2010) Membrane transporters in drug development. Nat Rev Drug Discov 9(3):215–236. https://doi.org/10.1038/nrd3028

Fotiadis D, Kanai Y, Palacín M (2013) The SLC3 and SLC7 families of amino acid transporters. Mol Aspects Med 34:139–158

CAS  PubMed  Google Scholar 

Molina-Arcas M, Casado F, Pastor-Anglada M (2009) Nucleoside transporter proteins. Curr Vasc Pharmacol 7:426. https://doi.org/10.2174/157016109789043892

Article  CAS  PubMed  Google Scholar 

Oda K, Hosoda N, Endo H et al (2010) L-Type amino acid transporter 1 inhibitors inhibit tumor cell growth. Cancer Sci 101. https://doi.org/10.1111/j.1349-7006.2009.01386.x

Koppula P, Zhang Y, Zhuang L, Gan B (2018) Amino acid transporter SLC7A11/ xCT at the crossroads of regulating redox homeostasis and nutrient dependency of cancer. Cancer Commun. https://doi.org/10.1186/s40880-018-0288-x

Article  Google Scholar 

Nies AT, Koepsell H, Damme K, Schwab M (2010) Organic cation transporters (OCTs, MATEs), in vitro and in vivo evidence for the importance in drug therapy. Drug Transport 105–167. https://doi.org/10.1007/978-3-642-14541-4_3

Jiang Z, Dong X, Yan X et al (2018) Nanogels of dual inhibitor-modified hyaluronic acid function as a potent inhibitor of amyloid β-protein aggregation and cytotoxicity. Sci Rep. https://doi.org/10.1038/s41598-018-21933-6

Article  PubMed  PubMed Central  Google Scholar 

He J, Wang X, Chen K et al (2022) The amino acid transporter SLC7A11-mediated crosstalk implicated in cancer therapy and the tumor microenvironment. Biochem Pharmacol 205:115241

CAS  PubMed  Google Scholar 

Pavlova NN, Thompson CB (2016) The emerging hallmarks of cancer metabolism. Cell Metab 23(1):27–47. https://doi.org/10.1016/j.cmet.2015.12.006

Altman BJ, Stine ZE, Dang CV (2016) From Krebs to clinic: glutamine metabolism to cancer therapy. Nat Rev Cancer. https://doi.org/10.1038/nrc.2016.71

Article  PubMed  PubMed Central  Google Scholar 

Van Geldermalsen M, Wang Q, Nagarajah R et al (2016) ASCT2/SLC1A5 controls glutamine uptake and tumour growth in triple-negative basal-like breast cancer. Oncogene 35:3201. https://doi.org/10.1038/onc.2015.381

Article  CAS  PubMed  Google Scholar 

Stockwell BR, Friedmann Angeli JP, Bayir H et al (2017) Ferroptosis: a regulated cell death nexus linking metabolism, redox biology, and disease. Cell 171(2):273–285

Nicklin P, Bergman P, Zhang B et al (2009) Bidirectional transport of amino acids regulates mTOR and autophagy. Cell. https://doi.org/10.1016/j.cell.2008.11.044

Article  PubMed  PubMed Central  Google Scholar 

Lopes C, Pereira C, Medeiros R (2021) ASCT2 and LAT1 contribution to the hallmarks of cancer: from a molecular perspective to clinical translation. Cancers (Basel). https://doi.org/10.3390/cancers13020203

Article  PubMed  PubMed Central  Google Scholar 

Martinez-Outschoorn UE, Peiris-Pagés M, Pestell RG et al (2017) Cancer metabolism: a therapeutic perspective. Nat Rev Clin Oncol 14(1):11–31

Bröer S (2014) The SLC38 family of sodium-amino acid co-transporters. Pflugers Arch Eur J Physiol 466:155–172

Palmieri F (2013) The mitochondrial transporter family SLC25: identification, properties and physiopathology. Mol Aspects Med 34:465–484

CAS  PubMed  Google Scholar 

Koepsell H (2020) Organic cation transporters in health and disease. Pharmacol Rev 72:253. https://doi.org/10.1124/pr.118.015578

Article 

Comments (0)

No login
gif