Progress in The Relationship Between Metabolic Enzyme of Gemcitabine and Chemotherapeutic Resistance of Pancreatic Cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

YUAN Tian ^1,2 , LIAO Quan ² , ZHAO Yupei ²

1.Peking Union Medical College, Chinese Academy of Medical Science, Beijing 100730, China;;
2.Department of General Surgery, Peking Union Hospital, Chinese Academy of Medical Science, Beijing 100730, China;

Corresponding author：

Keywords：

Pancreatic cancer; Gemcitabine; Metabolic enzyme; Resistance; Chemotherapy

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To introduce the research progress in the effect of chemotherapeutic resistance of metabolic enzymes of gemcitabine to pancreatic cancer.
Methods Recent literatures about metabolic enzymes that played key roles in mediating gemcitabine chemotherapeutic resistance of pancreatic cancer were collected and reviewed.
Results The metabolic enzymes of gemcitabine, such as hENT1, dCK, RRM1 and CDA, were closely related to chemotherapeutic resistance of pancreatic cancer. The relationship between the single nucleotide polymorphism of metabolic enzymes and the resistance to gemcitabine remained to be clarified.
Conclusion Multiple factors are involved in the mechanism of chemotherapeutic resistance of pancreatic cancer to gemcitabine, which needs further research.

Citation： YUAN Tian ,LIAO Quan,ZHAO Yupei. Progress in The Relationship Between Metabolic Enzyme of Gemcitabine and Chemotherapeutic Resistance of Pancreatic Cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2009, 16(8): 613-616. doi: Copy

1.	Alexakis N, Halloran C, Raraty M, et al. Current standards of surgery for pancreatic cancer [Ｊ]. Br J Surg, 2004; 91(11): 1410-1427.
2.	Abbruzzese JL. New applications of gemcitabine and future directions in the management of pancreatic cancer [Ｊ]. Cancer, 2002; 95 (4 Suppl): 941-945.
3.	Burris HA 3rd, Moore MJ, Andersen J, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial [Ｊ]. J Clin Oncol, 1997; 15(6): 2403-2413.
4.	Mini E, Nobili S, Caciagli B, et al. Cellular pharmacology of gemcitabine [Ｊ]. Ann Oncol, 2006; 17 (Suppl 5): v7-v12.
5.	Galmarini CM, Mackey JR, Dumontet C. Nucleoside analogues: mechanisms of drug resistance and reversal strategies [Ｊ]. Leukemia, 2001; 15(6): 875-890.
6.	Shi JY, Shi ZZ, Zhang SJ, et al. Association between single nucleotide polymorphisms in deoxycytidine kinase and treatment response among acute myeloid leukaemia patients [Ｊ]. Pharmacogenetics, 2004; 14(11): 759-768.
7.	Ward JL, Leung GP, Toan SV, et al. Functional analysis of site-directed glycosylation mutants of the human equilibrative nucleoside transporter-2 [Ｊ]. Arch Biochem Biophys, 2003; 411(1): 19-26.
8.	García-Manteiga J, Molina-Arcas M, Casado FJ, et al. Nucleoside transporter profiles in human pancreatic cancer cells: role of hCNT1 in 2’, 2’-difluorodeoxycytidine-induced cytotoxicity [Ｊ]. Clin Cancer Res, 2003; 9(13): 5000-5008.
9.	Mori R, Ishikawa T, Ichikawa Y, et al. Human equilibrative nucleoside transporter 1 is associated with the chemosensitivity of gemcitabine in human pancreatic adenocarcinoma and biliary tract carcinoma cells [Ｊ]. Oncol Rep, 2007; 17(5): 1201-1205.
10.	Rauchwerger DR, Firby PS, Hedley DW, et al. Equilibrative-sensitive nucleoside transporter and its role in gemcitabine sensitivity [Ｊ]. Cancer Res, 2000; 60(21): 6075-6079.
11.	Giovannetti E, Del Tacca M, Mey V, et al. Transcription analysis of human equilibrative nucleoside transporter-1 predicts survival in pancreas cancer patients treated with gemcitabine [Ｊ]. Cancer Res, 2006; 66(7): 3928-3935.
12.	Farrell JJ, Elsaleh H, Garcia M, et al. Human equilibrative nucleoside transporter 1 levels predict response to gemcitabine in patients with pancreatic cancer [Ｊ]. Gastroenterology, 2009; 136(1): 187-195.
13.	Spratlin J, Sangha R, Darry Glubrecht D, et al. The absence of human equilibrative nucleoside transporter 1 is associated with reduced survival in patients with gemcitabine-treated pancreas adenocarcinoma [Ｊ]. Clin Cancer Res, 2004; 10(20): 6956-6961.
14.	Giovannetti E, Mey V, Nannizzi S, et al. Pharmacogenetics of anticancer drug sensitivity in pancreatic cancer [Ｊ]. Mol Cancer Ther, 2006; 5(6): 1387-1395.
15.	Kroep JR, Loves WJ, van der Wilt CL, et al. Pretreatment deoxycytidine kinase levels predict in vivo gemcitabine sensitivity [Ｊ]. Mol Cancer Ther, 2002; 1(6): 371-376.
16.	Blackstock AW, Lightfoot H, Case LD, et al. Tumor uptake and elimination of 2’, 2’-difluoro-2’-deoxycytidine (gemcitabine) after deoxycytidine kinase gene transfer: correlation with in vivo tumor response [Ｊ]. Clin Cancer Res, 2001; 7(10): 3263-3268.
17.	Veuger MJ, Heemskerk MH, Honders MW, et al. Functional role of alternatively spliced deoxycytidine kinase in sensitivity to cytarabine of acute myeloid leukemic cells [Ｊ]. Blood, 2002; 99(4): 1373-1380.
18.	Veuger MJ, Honders MW, Landegent JE, et al. High incidence of alternatively spliced forms of deoxycytidine kinase in patients with resistant acute myeloid leukemia [Ｊ]. Blood, 2000; 96(4): 1517-1524.
19.	Galmarini CM, Clarke ML, Jordheim L, et al. Resistance to gemcitabine in a human follicular lymphoma cell line is due to partial deletion of the deoxycytidine kinase gene [Ｊ]. BMC Pharmacol, 2004; 4: 8-20.
20.	Ohhashi S, Ohuchida K, Mizumoto K, et al. Down-regulation of deoxycytidine kinase enhances acquired resistance to gemcitabine in pancreatic cancer [Ｊ]. Anticancer Res, 2008; 28(4B): 2205-2212.
21.	Szantai E, Ronai Z, Sasvari-Szekely M, et al. Multicapillary electrophoresis analysis of single-nucleotide sequence variations in the deoxycytidine kinase gene [Ｊ]. Clin Chem, 2006; 52(9): 1756-1762.
22.	Sebastiani V, Ricci F, Rubio-Viqueira B, et al. Immunohistochemical and genetic evaluation of deoxycytidine kinase in pancreatic cancer: relationship to molecular mechanisms of gemcitabine resistance and survival [Ｊ]. Clin Cancer Res, 2006; 12(8): 2492-2497.
23.	Davidson JD, Ma L, Flagella M, et al. An increase in the expression of ribonucleotide reductase large subunit 1 is associated with gemcitabine resistance in non-small cell lung cancer cell lines [Ｊ]. Cancer Res, 2004; 64(11): 3761-3766.
24.	Bergman AM, Eijk PP, Ruiz van Haperen VW, et al. In vivo induction of resistance to gemcitabine resultsin increased expression of ribonucleotide reductase subunit M1 as the major determinant [Ｊ]. Cancer Res, 2005; 65(20): 9510-9516.
25.	Guex N, Peitsch MC. SWISS-MODEL and the Swiss-PdbViewer: an environment for comparative protein modeling [Ｊ]. Electrophoresis, 1997; 18(15): 2714-2723.
26.	Yonemori K, Ueno H, Okusaka T, et al. Severe drug toxicity associated with a single-nucleotide polymorphism of the cytidine deaminase gene in a Japanese cancer patient treated with gemcitabine plus cisplatin [Ｊ]. Clin Cancer Res, 2005; 11(7): 2620-2624.
27.	Sugiyama E, Kaniwa N, Kim SR, et al. Pharmacokinetics of gemcitabine in Japanese cancer patients: the impact of a cytidine deaminase polymorphism [Ｊ]. J Clin Oncol, 2007; 25(1): 32-42.
28.	Nakano Y, Tanno S, Koizumi K, et al. Gemcitabine chemoresistance and molecular markers associated with gemcitabine transport and metabolism in human pancreatic cancer cells [Ｊ]. Br J Cancer, 2007; 96(3): 457-463.
29.	张立阳，赵玉沛，吴元德，等. 胰腺癌阿霉素耐药细胞株SW1990/ADM的建立及其耐药机理研究 [Ｊ]. 中国普外基础与临床杂志， 2005； 12（1）： 46-50.
30.	潘博，郭俊超，廖泉，等. 吉西他滨与胰腺癌化疗耐药 [Ｊ]. 中国普外基础与临床杂志， 2005； 12（5）： 530-532.

1. Alexakis N, Halloran C, Raraty M, et al. Current standards of surgery for pancreatic cancer [Ｊ]. Br J Surg, 2004; 91(11): 1410-1427.
2. Abbruzzese JL. New applications of gemcitabine and future directions in the management of pancreatic cancer [Ｊ]. Cancer, 2002; 95 (4 Suppl): 941-945.
3. Burris HA 3rd, Moore MJ, Andersen J, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial [Ｊ]. J Clin Oncol, 1997; 15(6): 2403-2413.
4. Mini E, Nobili S, Caciagli B, et al. Cellular pharmacology of gemcitabine [Ｊ]. Ann Oncol, 2006; 17 (Suppl 5): v7-v12.
5. Galmarini CM, Mackey JR, Dumontet C. Nucleoside analogues: mechanisms of drug resistance and reversal strategies [Ｊ]. Leukemia, 2001; 15(6): 875-890.
6. Shi JY, Shi ZZ, Zhang SJ, et al. Association between single nucleotide polymorphisms in deoxycytidine kinase and treatment response among acute myeloid leukaemia patients [Ｊ]. Pharmacogenetics, 2004; 14(11): 759-768.
7. Ward JL, Leung GP, Toan SV, et al. Functional analysis of site-directed glycosylation mutants of the human equilibrative nucleoside transporter-2 [Ｊ]. Arch Biochem Biophys, 2003; 411(1): 19-26.
8. García-Manteiga J, Molina-Arcas M, Casado FJ, et al. Nucleoside transporter profiles in human pancreatic cancer cells: role of hCNT1 in 2’, 2’-difluorodeoxycytidine-induced cytotoxicity [Ｊ]. Clin Cancer Res, 2003; 9(13): 5000-5008.
9. Mori R, Ishikawa T, Ichikawa Y, et al. Human equilibrative nucleoside transporter 1 is associated with the chemosensitivity of gemcitabine in human pancreatic adenocarcinoma and biliary tract carcinoma cells [Ｊ]. Oncol Rep, 2007; 17(5): 1201-1205.
10. Rauchwerger DR, Firby PS, Hedley DW, et al. Equilibrative-sensitive nucleoside transporter and its role in gemcitabine sensitivity [Ｊ]. Cancer Res, 2000; 60(21): 6075-6079.
11. Giovannetti E, Del Tacca M, Mey V, et al. Transcription analysis of human equilibrative nucleoside transporter-1 predicts survival in pancreas cancer patients treated with gemcitabine [Ｊ]. Cancer Res, 2006; 66(7): 3928-3935.
12. Farrell JJ, Elsaleh H, Garcia M, et al. Human equilibrative nucleoside transporter 1 levels predict response to gemcitabine in patients with pancreatic cancer [Ｊ]. Gastroenterology, 2009; 136(1): 187-195.
13. Spratlin J, Sangha R, Darry Glubrecht D, et al. The absence of human equilibrative nucleoside transporter 1 is associated with reduced survival in patients with gemcitabine-treated pancreas adenocarcinoma [Ｊ]. Clin Cancer Res, 2004; 10(20): 6956-6961.
14. Giovannetti E, Mey V, Nannizzi S, et al. Pharmacogenetics of anticancer drug sensitivity in pancreatic cancer [Ｊ]. Mol Cancer Ther, 2006; 5(6): 1387-1395.
15. Kroep JR, Loves WJ, van der Wilt CL, et al. Pretreatment deoxycytidine kinase levels predict in vivo gemcitabine sensitivity [Ｊ]. Mol Cancer Ther, 2002; 1(6): 371-376.
16. Blackstock AW, Lightfoot H, Case LD, et al. Tumor uptake and elimination of 2’, 2’-difluoro-2’-deoxycytidine (gemcitabine) after deoxycytidine kinase gene transfer: correlation with in vivo tumor response [Ｊ]. Clin Cancer Res, 2001; 7(10): 3263-3268.
17. Veuger MJ, Heemskerk MH, Honders MW, et al. Functional role of alternatively spliced deoxycytidine kinase in sensitivity to cytarabine of acute myeloid leukemic cells [Ｊ]. Blood, 2002; 99(4): 1373-1380.
18. Veuger MJ, Honders MW, Landegent JE, et al. High incidence of alternatively spliced forms of deoxycytidine kinase in patients with resistant acute myeloid leukemia [Ｊ]. Blood, 2000; 96(4): 1517-1524.
19. Galmarini CM, Clarke ML, Jordheim L, et al. Resistance to gemcitabine in a human follicular lymphoma cell line is due to partial deletion of the deoxycytidine kinase gene [Ｊ]. BMC Pharmacol, 2004; 4: 8-20.
20. Ohhashi S, Ohuchida K, Mizumoto K, et al. Down-regulation of deoxycytidine kinase enhances acquired resistance to gemcitabine in pancreatic cancer [Ｊ]. Anticancer Res, 2008; 28(4B): 2205-2212.
21. Szantai E, Ronai Z, Sasvari-Szekely M, et al. Multicapillary electrophoresis analysis of single-nucleotide sequence variations in the deoxycytidine kinase gene [Ｊ]. Clin Chem, 2006; 52(9): 1756-1762.
22. Sebastiani V, Ricci F, Rubio-Viqueira B, et al. Immunohistochemical and genetic evaluation of deoxycytidine kinase in pancreatic cancer: relationship to molecular mechanisms of gemcitabine resistance and survival [Ｊ]. Clin Cancer Res, 2006; 12(8): 2492-2497.
23. Davidson JD, Ma L, Flagella M, et al. An increase in the expression of ribonucleotide reductase large subunit 1 is associated with gemcitabine resistance in non-small cell lung cancer cell lines [Ｊ]. Cancer Res, 2004; 64(11): 3761-3766.
24. Bergman AM, Eijk PP, Ruiz van Haperen VW, et al. In vivo induction of resistance to gemcitabine resultsin increased expression of ribonucleotide reductase subunit M1 as the major determinant [Ｊ]. Cancer Res, 2005; 65(20): 9510-9516.
25. Guex N, Peitsch MC. SWISS-MODEL and the Swiss-PdbViewer: an environment for comparative protein modeling [Ｊ]. Electrophoresis, 1997; 18(15): 2714-2723.
26. Yonemori K, Ueno H, Okusaka T, et al. Severe drug toxicity associated with a single-nucleotide polymorphism of the cytidine deaminase gene in a Japanese cancer patient treated with gemcitabine plus cisplatin [Ｊ]. Clin Cancer Res, 2005; 11(7): 2620-2624.
27. Sugiyama E, Kaniwa N, Kim SR, et al. Pharmacokinetics of gemcitabine in Japanese cancer patients: the impact of a cytidine deaminase polymorphism [Ｊ]. J Clin Oncol, 2007; 25(1): 32-42.
28. Nakano Y, Tanno S, Koizumi K, et al. Gemcitabine chemoresistance and molecular markers associated with gemcitabine transport and metabolism in human pancreatic cancer cells [Ｊ]. Br J Cancer, 2007; 96(3): 457-463.
29. 张立阳，赵玉沛，吴元德，等. 胰腺癌阿霉素耐药细胞株SW1990/ADM的建立及其耐药机理研究 [Ｊ]. 中国普外基础与临床杂志， 2005； 12（1）： 46-50.
30. 潘博，郭俊超，廖泉，等. 吉西他滨与胰腺癌化疗耐药 [Ｊ]. 中国普外基础与临床杂志， 2005； 12（5）： 530-532.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Progress in The Relationship Between Metabolic Enzyme of Gemcitabine and Chemotherapeutic Resistance of Pancreatic Cancer

Abstract Full text Figures/Tables Video References Cited by

Format

Content