Human equilibrative nucleoside transporter 1 (hENT1) in pancreatic adenocarcinoma: Towards individualized treatment decisions

Cancers

Volumn 2, Issue 4, 2010, Pages 2044-2054

  Spratlin, Jennifer L ^a   Mackey, John R ^a  

^a UNIVERSITY OF ALBERTA   (Canada)

Author keywords

hENT1; Individualized medicine; Nucleoside transporters; Pancreatic adenocarcinoma; Predictive tool

Indexed keywords

EQUILIBRATIVE NUCLEOSIDE TRANSPORTER 1; FLUOROURACIL; GEMCITABINE;

ANTINEOPLASTIC ACTIVITY; CANCER RADIOTHERAPY; CANCER RESISTANCE; CANCER STAGING; CANCER SURVIVAL; CYTOTOXICITY; DISEASE FREE SURVIVAL; DRUG EFFICACY; DRUG METABOLISM; DRUG POTENTIATION; DRUG PROTEIN BINDING; DRUG TARGETING; DRUG TRANSPORT; HUMAN; IC 50; MEDICAL DECISION MAKING; OVERALL SURVIVAL; PANCREAS ADENOCARCINOMA; PROGNOSIS; PROTEIN DETERMINATION; PROTEIN EXPRESSION; PROTEIN FUNCTION; REVIEW; SINGLE NUCLEOTIDE POLYMORPHISM; SURVIVAL TIME;

EID: 79952260997     PISSN: None     EISSN: 20726694     Source Type: Journal    
DOI: 10.3390/cancers2042044     Document Type: Review

References (46)

1. Jemal, A.; Siegel, R.; Xu, J.; Ward, E. Cancer Statistics, 2010. CA Cancer J. Clin. 2010, doi: 10.3322/caac.20073.
2. Yeo, T.P.; Hruban R.H.; Leach S.D.; Wilentz R.E.; Sohn T.A.; Kern S.E.; Iacobuzio-Donahue C.A.; Maitra A.; Goggins M.; Canto M.I.; et al. Pancreatic cancer. Curr. Probl. Cancer 2002, 26, 176-275.
3. Burris, H.A., 3rd; Moore, M.J.; Andersen, J.; Green, M.R.; Rothenberg, M.L.; Modiano, M.R.; Cripps, M.C.; Portenoy, R.K.; Storniolo, A.M.; Tarassoff, P.; et al. Improvements in Survival and Clinical Benefit with Gemcitabine as First-Line Therapy for Patients with Advanced Pancreas Cancer: A Randomized Trial. J. Clin. Oncol. 1997, 15, 2403-2413.
4. Conroy, T.; Desseigne, F.; Ychou, M.; Ducreux, M.; Bouche, O.; Guimbaud, R.; Becouarn, Y.; Montoto-Grillot, C.; Gourgou-Bourgade, S.; Adenis, A. Randomized Phase III Trial Comparing FOLFIRINOX (F: 5FU/leucovorin [LV], irinotecan [I], and oxaliplatin [O]) versus Gemcitabine (G) as First-Line Treatment for Metastatic Pancreatic Adenocarcinoma (MPA): Preplanned Interim Analysis Results of the PRODIGE 4/ACCORD 11 trial. J. Clin. Oncol. 2010, 28, Abstr. 4010.
5. Pelzer, U.; Kubica, K.; Stieler, J.; Schwaner, I.; Heil, G.; Görner, M.; Mölle, M.; Hilbig, A.; Dörken, B.; Riess, H.; et al. A Randomized Trial in Patients with Gemcitabine Refractory Pancreatic Cancer. Final Results of the CONKO 003 Study. J. Clin. Oncol. 2008, 26, Abstr. 4508.
6. Moore, M.J.; Goldstein, D.; Hamm, J.; Figer, A.; Hecht, J.R.; Gallinger, S.; Au, H.J.; Murawa, P.; Walde, D.; Wolff, R.A.; et al. Erlotinib plus Gemcitabine Compared with Gemcitabine alone in Patients with Advanced Pancreatic Cancer: A Phase III Trial of the National Cancer Institute of Canada Clinical Trials Group. J. Clin. Oncol. 2007, 25, 1960-1966.
7. Philip, P.A.; Benedetti, J.; Corless, C.L.; Wong, R.; O'Reilly, E.M.; Flynn, P.J.; Rowland, K.M.; Atkins, J.N.; Mirtsching, B.C.; Rivkin, S.E.; et al. Phase III Study Comparing Gemcitabine plus Cetuximab versus Gmcitabine in Patients with Advanced Pancreatic Adenocarcinoma: Southwest Oncology Group-Directed Intergroup Trial S0205. J. Clin. Oncol. 2010, 28, 3605-3610.
8. Kindler, H.L.; Niedzwiecki, D.; Hollis, D.; Sutherland, S.; Schrag, D.; Hurwitz, H.; Innocenti, F.; Mulcahy, M.F.; O'Reilly, E.; Wozniak, T.F. et al. Gemcitabine plus Bevacizumab Compared with Gemcitabine plus Placebo in Patients with Advanced Pancreatic Cancer: Phase III Trial of the Cancer and Leukemia Group B (CALGB 80303). J. Clin. Oncol. 2010, 28, 3617-3622.
9. O'Reilly, E.M.; Niedzwiecki, D.; Hollis, D.R.; Bekaii-Saab, T.S.; Pluard, T.; Duffy, A.; Overcash, F.; Ivy, S.P.; Goldberg, R.M. A Phase II Trial of Sunitinib (S) in Previously-Treated Pancreas Adenocarcinoma (PAC), CALGB 80603. J. Clin. Oncol. 2008, 26, Abstr. 4515.
10. Wallace, J.A.; Locker, G.; Nattam, S.; Kasza, K.; Wade-Oliver, K.; Stadler, W.M.; Vokes, E.E.; Kindler, H.L. Sorafenib (S) plus Gemcitabine (G) for Advanced Pancreatic Cancer (PC): A Phase II Trial of the University of Chicago Phase II Consortium. J. Clin. Oncol 2007, 25, Abstract 4608.
11. Wolp, B.M.; Hezel, A.F.; Abrams, T.; Blaszkowsky, L.S.; Meyerhardt, J.A.; Chan, J.A.; Enzinger, P.C.; Allen, B.; Clark, J.W.; Ryan, D.P.; et al. Oral mTOR Inhibitor Everolimus in Patients with Gemcitabine-Refractory Metastatic Pancreatic Cancer. J. Clin. Oncol. 2009, 27, 193-198.
12. Bramhall, S.R.; Schulz, J.; Nemunaitis, J.; Brown, P.D.; Baillet, M.; Buckels, J.A. A Double- Blind Placebo-Controlled, Randomised Study Comparing Gemcitabine and Marimastat with Gemcitabine and Placebo as First Line Therapy in Patients with Advanced Pancreatic Cancer. Br. J. Cancer 2002, 87, 161-167.
13. Moore, M.J.; Hamm, J.; Dancey, J.; Eisenberg, P.D.; Dagenais, M.; Fields, A.; Hagan, K.; Greenberg, B.; Colwell, B.; Zee, B.; et al. Comparison of Gemcitabine versus the Matrix Metalloproteinase Inhibitor BAY 12-9566 in Patients with Advanced or Metastatic Adenocarcinoma of the Pancreas: A Phase III Trial of the National Cancer Institute of Canada Clinical Trials Group. J. Clin. Oncol. 2003, 21, 3296-3302.
14. Kindler, H.L.; Gangadhar, T.; Karrison, T.; Hochster, H.S.; Moore, M.J.; Micetich, K.; Sun, W.; Catenacci, D.V.; Stadler, W.M.; Vokes, E.E. Final Analysis of a Randomized Phase II Study of Bevacizumab (B) and Gemcitabine (G) plus Cetuximab (C) or Erlotinib (E) in Patients (pts) with Advanced Pancreatic Cancer (PC). J. Clin. Oncol. 2008, 26, Abstr 4502.
15. Vervenn, W.; Bennouna, J.; Humblet, Y.; Gill, S.; Moore, M.J.; Laethem, J.V.; Shang, A.; Cosaert, J.; Verslype, C.; van Cutsem, E. A Randomized Double-Blind Placebo (P) Controlled Multicenter Phase III Trial to Evaluate the Efficacy and Safety of Adding Bevacizumab (B) to Erlotinib (E) and Gemcitabine (G) in Patients (pts) with Metastatic Pancreatic Cancer. J. Clin. Oncol. 2008, 26, Abstr.4507.
16. Tanaka, M.; Javle, M.; Dong, X.; Eng, C.; Abbruzzese, J.L.; Li, D. Gemcitabine Metabolic and Transporter gene Polymorphisms are Associated with Drug Toxicity and Efficacy in Patients with Locally Advanced Pancreatic Cancer. Cancer 2010, 116, 5325-5335.
17. Tempero, M.; Plunkett, W.; Ruiz, Van Haperen, V.; Hainsworth, J.; Hochster, H.; Lenzi, R.; Abbruzzese, J. Randomized Phase II comparison Of Dose-Intense Gemcitabine: Thirty-minute Infusion and fixed Dose rate Infusion in Patients with Pancreatic Adenocarcinoma. J. Clin. Oncol. 2003, 21, 3402-3408.
18. Galmarini, C.M.; Mackey, J.R.; Dumontet, C. Nucleoside Analogues: Mechanisms of Drug Resistance and Reversal Strategies. Leukemia 2001, 15, 875-890.
19. Mackey, J.R.; Baldwin, S.A.; Young, J.D.; Cass, C.E. Nucleoside Transport and its Significance for Anticancer Drug Resistance. Drug Resist. Updat. 1998, 1, 310-324.
20. Young, J.D.; Yao, S.Y.; Sun, L.; Cass, C.E.; Baldwin, S.A. Human Equilibrative Nucleoside Transporter (ENT) Family of Nucleoside and Nucleobase Transporter Proteins. Xenobiotica 2008, 38, 995-1021.
21. Ritzel, M.W.; Ng, A.M.; Yao, S.Y.; Graham, K.; Loewen, S.K.; Smith, K.M.; Ritzel, R.G.; Mowles, D.A.; Carpenter, P.; Chen, X.Z.; et al. Molecular Identification and Characterization of Novel Human and Mouse Concentrative Na+-Nucleoside Cotransporter Proteins (hCNT3 and mCNT3) Broadly Selective for Purine and Pyrimidine Nucleosides (system cib). J. Biol. Chem. 2001, 276, 2914-2927.
22. Ritzel, M.W.; Ng, A.M.; Yao, S.Y.; Graham, K.; Loewen, S.K.; Smith, K.M.; Hyde, R.J.; Karpinski, E.; Cass, C.E.; Baldwin, S.A.; et al. Recent Molecular Advances in Studies of the Concentrative Na+-Dependent Nucleoside Transporter (CNT) Family: Identification and Characterization of Novel Human and Mouse Proteins (hCNT3 and mCNT3) Broadly Selective for Purine and Pyrimidine Nucleosides (system cib). Mol. Membr. Biol. 2001, 18, 65-72.
23. Mackey, J.R.; Yao, S.Y.; Smith, K.M.; Karpinski, E.; Baldwin, S.A.; Cass, C.E.; Young, J.D. Gemcitabine Transport in Xenopus Oocytes Expressing Recombinant Plasma Membrane Mammalian Nucleoside Transporters. J. Natl. Cancer Inst. 1999, 911, 876-1881.
24. Mackey, J.R.; Mani, R.S.; Selner, M.; Mowles, D.; Young, J.D.; Belt, J.A.; Crawford, C.R.; Cass, C.E. Functional Nucleoside Transporters are Required for Gemcitabine Influx and Manifestation of Toxicity in Cancer Cell Lines. Cancer Res. 1998, 58, 4349-4357.
25. Garcia-Manteiga, J.; Molina-Arcas, M.; Casado, F.J.; Mazo, A.; Pastor-Anglada, M. Nucleoside Transporter Profiles in Human Pancreatic Cancer Cells: Role of hCNT1 in 2', 2'- Difluorodeoxycytidine- Induced Cytotoxicity. Clin. Cancer Res. 2003, 9, 5000-5008.
26. Wiley, J.S.; Jones, S.P.; Sawyer, W.H.; Paterson, A.R. Cytosine Arabinoside Influx and Nucleoside Transport Sites in Acute Leukemia. J. Clin. Invest. 1982, 69, 479-489.
27. Wiley, J.S.; Jones, S.P.; Sawyer, W.H. Cytosine Arabinoside Transport by Human Leukaemic Cells. Eur. J. Cancer Clin. Oncol 1983, 19, 1067-1074.
28. Paproski, R.J.; Wuest, M.; Jans, H.S.; Graham, K.; Gati, W.P.; McQuarrie, S.; McEwan, A.; Mercer, J.; Young, J.D.; Cass, C.E. Biodistribution and Uptake of 3'-Deoxy-3'-Fluorothymidine in ENT1-Knockout Mice and in an ENT1-Knockdown Tumor Model. J. Nucl. Med. 2010, 51, 1447-1455.
29. Cass, C.E.; King, K.M.; Montano, J.T.; Janowska-Wieczorek, A. A Comparison of the Abilities of Nitrobenzyl Thioinosine, Dilazep, and Dipyridamole to Protect Human Hematopoietic Cells from 7-Deazaadenosine (tubercidin). Cancer Res. 1992, 52, 5879-5886.
30. Huang, P.; Plunkett, W. Induction of Apoptosis by Gemcitabine. Semin. Oncol. 1995, 22, 19-25.
31. Ruiz, van Haperen V.W.; Veerma, G.; Vermorke, J.B.; Peters, G.J. 2', 2'-Difluoro-deoxycytidine (Gemcitabine) Incorporation into RNA and DNA of Tumour Cell Lines. Biochem. Pharmacol. 1993, 46, 762-766.
32. Plunkett, W.; Huang, P.; Searcy, C.E.; Gandhi, V. Gemcitabine: Preclinical Pharmacology and Mechanisms of Action. Semin. Oncol. 1996, 23, 3-15.
33. Heinemann, V.; Schulz, L.; Issels, R.D.; Plunkett, W. Gemcitabine: A Modulator of Intracellular Nucleotide and Deoxynucleotide Metabolism. Semin. Oncol. 1995, 22, 11-18.
34. Spratlin, J.; Sangha, R.; Glubrecht, D.; Dabbagh, L.; Young, J.D.; Dumontet, C.; Cass, C.; Lai, R.; Mackey, J.R. The Absence of Human Equilibrative Nucleoside Transporter 1 is Associated with Reduced Survival in Patients with Gemcitabine-Treated Pancreas Adenocarcinoma. Clin. Cancer Res. 2004, 10, 6956-6961.
35. Mori, R.; Ishikawa, T.; Ichikawa, Y.; Taniguchi, K.; Matsuyama, R.; Ueda, M.; Fujii, Y.; Endo, I.; Togo, S.; Danenberg, P.V.; et al. Human Equilibrative Nucleoside Transporter 1 is Associated with the Chemosensitivity of Gemcitabine in Human Pancreatic Adenocarcinoma and Biliary Tract carcinoma Cells. Oncol. Rep. 2007, 17, 1201-1205.
36. Nakano, Y.; Tanno, S.; Koizumi, K.; Nishikawa, T.; Nakamura, K.; Minoguchi, M.; Izawa, T.; Mizukami, Y.; Okumura, T.; Kohgo, Y. Gemcitabine Chemoresistance and Molecular Markers Associated with Gemcitabine Transport and Metabolism in Human Pancreatic Cancer Cells. Br. J. Cancer 2007, 96, 457-463.
37. Giovannett, E.; Del Tacca, M.; Mey, V.; Funel, N.; Nannizzi, S.; Ricci, S.; Orlandini, C.; Boggi, U.; Campani, D.; Del Chiaro, M.; et al. Transcription Analysis of Human Equilibrative Nucleoside Transporter-1 Predicts Survival in Pancreas Cancer Patients Treated with Gemcitabine. Cancer Res. 2006, 66, 3928-3935.
38. Marechal, R.; Mackey, J.R.; Lai, R.; Demetter, P.; Peeters, M.; Polus, M.; Cass, C.E.; Young, J.; Salmon, I.; Deviere, J.; et al. Human Equilibrative Nucleoside Transporter 1 and Human Concentrative Nucleoside Transporter 3 Predict Survival after Adjuvant Gemcitabine Therapy in Resected Pancreatic Adenocarcinoma. Clin. Cancer Res. 2009, 15, 2913-2919.
39. Regine, W.F.; Winter, K.A.; Abrams, R.A; Safran, H.; Hoffman, J.P.; Konski, A.; Benson, A.B.; Macdonald, J.S.; Kudrimoti, M.R.; Fromm, M.L.; et al. Fluorouracil vs Gemcitabine Chemotherapy before and after Fluorouracil-Based Chemoradiation Following Resection of Pancreatic Adenocarcinoma: A Randomized Controlled Trial. JAMA 2008, 299, 1019-1026.
40. Farrell, J.J.; Elsaleh, H.; Garcia, M.; Lai, R.; Ammar, A.; Regine, W.F.; Abrams, R.; Benson, A.B.; Macdonald, J.; Cass, C.E.; et al. Human Equilibrative Nucleoside Transporter 1 Levels Predict Response to Gemcitabine in Patients with Pancreatic Cancer. Gastroenterology 2009, 136, 187-195.
41. Osato, D.H.; Huang, C.C.; Kawamoto, M.; Johns, S.J.; Stryke, D.; Wang, J.; Ferrin, T.E.; Herskowitz, I.; Giacomini, K.M. Functional Characterization in Yeast of Genetic Variants in the Human Equilibrative Nucleoside Transporter, ENT1. Pharmacogenetics 2003, 13, 297-301.
42. Kim, S.R.; Saito, Y.; Maekawa, K.; Sugiyama, E.; Kaniwa, N.; Ueno, H.; Okusaka, T.; Morizane, C.; Yamamoto, N.; Iked, A.M.; et al. Thirty Novel Genetic Variations in the SLC29A1 Gene Encoding Human Equilibrative Nucleoside Transporter 1 (hENT1). Drug Metab. Pharmacokinet. 2006, 21, 248-256.
43. Myers, S.N.; Goyal, R.K.; Roy, J.D.; Fairfull, L.D.; Wilson, J.W.; Ferrell, R.E. Functional Single Nucleotide Polymorphism Haplotypes in the Human Equilibrative Nucleoside Transporter 1. Pharmacogenet. Genomics 2006, 16, 315-320.
44. Okazaki, T.; Javle, M.; Tanaka, M.; Abbruzzese, J.L.; Li, D. Single Nucleotide Polymorphisms of Gemcitabine Metabolic Genes and Pancreatic Cancer Survival and Drug toxicity. Clin. Cancer Res. 2010, 16, 320-329.
45. Tabernero, J.; Macarulla, T. Changing the Paradigm in Conducting Randomized Clinical Studies in Advanced Pancreatic Cancer: An Opportunity for Better Clinical Development. J. Clin. Oncol. 2009, 27, 5487-5491.
46. Fujita, H.; Ohuchida, K.; Mizumoto, K.; Itaba, S.; Ito, T.; Nakata, K.; Yu, J.; Kayashima, T.; Souzaki, R.; Tajiri, T.; et al. Gene Expression Levels as Predictive Markers of Outcome in Pancreatic Cancer after Gemcitabine-Based Adjuvant Chemotherapy. Neoplasia 2010, 12, 807-817.