Mechanisms underlying gemcitabine resistance in pancreatic cancer and sensitisation by the iMiD™ lenalidomide

Anticancer Research

Volumn 31, Issue 11, 2011, Pages 3747-3756

  Fryer, Rosemary A ^a   Barlett, Blake ^b   Galustian, Christine ^a   Dalgleish, Angus G ^a  

^a UNIVERSITY COLLEGE LONDON   (United Kingdom)

^b CELGENE CORPORATION   (United States)

Author keywords

ERK; Gemcitabine; Lenalidomide; Pancreatic cancer; Resistance

Indexed keywords

1,4 DIAMINO 1,4 BIS(2 AMINOPHENYLTHIO) 2,3 DICYANOBUTADIENE; GEMCITABINE; LENALIDOMIDE; MITOGEN ACTIVATED PROTEIN KINASE;

ARTICLE; CANCER RESISTANCE; CELL LINE; CELL STRAIN BXPC 3; CELL STRAIN MIA PACA 2; CELL STRAIN PANC 1; CHEMOSENSITIVITY; CHEMOSENSITIZATION; COMBINATION CHEMOTHERAPY; CONTROLLED STUDY; DRUG POTENTIATION; ENZYME ACTIVATION; GENETIC TRANSFECTION; HUMAN; HUMAN CELL; IC 50; PANCREAS CANCER; PRIORITY JOURNAL; PROTEIN EXPRESSION; WESTERN BLOTTING;

ANTIMETABOLITES, ANTINEOPLASTIC; ANTINEOPLASTIC AGENTS; APOPTOSIS; BLOTTING, WESTERN; BUTADIENES; DEOXYCYTIDINE; DRUG RESISTANCE, NEOPLASM; DRUG SYNERGISM; ENZYME INHIBITORS; EXTRACELLULAR SIGNAL-REGULATED MAP KINASES; HUMANS; NITRILES; PANCREATIC NEOPLASMS; PHOSPHORYLATION; THALIDOMIDE; TUMOR CELLS, CULTURED;

EID: 83055179604     PISSN: 02507005     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (47)

1. Jemal A, Siegel R, Ward E, Murray T, Xu J and Thun MJ: Cancer Statistics, 2007. CA: a Cancer Journal for Clinicians 57: 43-66, 2007. (Pubitemid 46148091)
2. Sarkar FH, Banerjee S and Li Y: Pancreatic cancer: pathogenesis, prevention and treatment. Toxicol Appl Pharmacol 224: 326-336, 2006.
3. Burris HA 3rd, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, Cripps MC, Portenoy RK, Storniolo AM, Tarassoff P, Nelson R, Dorr FA, Stephens CD and Von Hoff DD: Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol 15: 2403-2413, 1997. (Pubitemid 27251144)
4. Akada M, Crnogorac-Jurcevic T, Lattimore S, Mahon P, Lopes R, Sunamura M, Matsuno S and Lemoine NR: Intrinsic chemoresistance to gemcitabine is associated with decreased expression of BNIP3 in pancreatic cancer. Clin Cancer Res 11: 3094-3101, 2005. (Pubitemid 40525216)
5. Hamacher R, Schmid RM and Saur D, Schneider G: Apoptotic pathways in pancreatic ductal adenocarcinoma. Mol Cancer 7: 64-74, 2008.
6. Wang W, Abbruzzese JL, Evans CB, Larry L, Cleary KR and Chiao PJ: The nuclear factor-kappa B RelA transcription factor is constitutively activated in human pancreatic adenocarcinoma cells. Clin Cancer Res 5: 119-127, 1999. (Pubitemid 29045184)
7. Ng SSW, Tsao MS, Chow S and Hedley DW: Inhibition of phosphatidylinositide 3-kinase enhances gemcitabine-induced apoptosis in human pancreatic cancer cells. Cancer Res 60: 5451-5455, 2000.
8. Ohhashi S, Ohuchida K, Mizumoto K, Fujita H, Egami T, Yu J, Toma H, Sadatomi S, Nagai E and Tanaka M: Down-regulation of deoxycytidine kinase enhances acquired resistance to gemcitabine in pancreatic cancer. Anticancer Res 28: 2205-2212, 2008.
9. He AR, Lindenberg AP and Marshall JL: Biologic therapies for advanced pancreatic cancer. Exp Rev Anticancer Ther 8: 1331-1338, 2008.
10. van Laethem J and Marechal R: Emerging drugs for the treatment of pancreatic cancer. Exp Opin Emerging Drugs 12: 301-311, 2007.
11. Mirmohammadsadegh A, Mota R, Gustrau A, Hassan M, Nambiar S, Marini A, Bojar H, Tannapfel A and Hengge UR: ERK1/2 is highly phosphorylated in melanoma metastases and protects melanoma cells from cisplatin-mediated apoptosis. J Invest Dermatol 127: 2207-2215, 2007. (Pubitemid 47258498)
12. Caja L, Sancho P, Bertran E, Iglesias-Serret D, Gil J and Fabergat I: Overactivation of the MEK/ERK pathway in liver tumour cells confers resistance to TGF-{beta}-induced cell death through impairing up-regulation of the NADPH oxidase NOX4. Cancer Res 69: 7595-7602, 2009.
13. Mhaidat NM, Alali FQ, Matalqah SM, Matalka II, Jaradat SA, Al-Sawalha NA and Thorne RF: Inhibition of MEK sensitizes paclitaxel-induced apoptosis of human colorectal cancer cells by downregulation of GRP78. Anticancer Drugs 20: 601-606, 2009.
14. Matsumoto K, Nagahara T, Okano J and Murawaki Y: The growth inhibition of hepatocellular and cholangiocellular carcinoma by gemcitabine and the roles of extracellular signal-regulated and checkpoint kinases. Oncol Rep 20: 863-872, 2008.
15. Bernhard J, Dietrich D, Scheithauer W, Gerber D, Bodoky G, Ruhstaller T, Glimelius B, Bajetta E, Schüller J, Saletti P, Bauer J, Figer A, Pestalozzi BC, Köhne CH, Mingrone W, Stemmer SM, Tàmas K, Kornek GV, Koeberle D and Herrmann R; Central European Cooperative Oncology Group. Clinical benefit and quality of life in patients with advanced pancreatic cancer receiving gemcitabine plus capecitabine versus gemcitabine alone: a randomized multicenter phase III clinical trial-SAKK 44/00-CECOG/PAN.1.3.001. J Clin Oncol 26: 3965-3701, 2008.
16. Cunningham D, Chau I, Stocken DD, Valle JW, Smith D, Steward W, Harper PG, Dunn J, Tudur-Smith C, West J, Falk S, Crellin A, Adab F, Thompson J, Leonard P, Ostrowski J, Eatock M, Scheithauer W, Herrmann R and Neoptolemos JP: Phase III randomized comparison of gemcitabine versus gemcitabine plus capecitabine in patients with advanced pancreatic cancer. J Clin Oncol 27: 5513-5518, 2009.
17. Dragovich T, Huberman M, Von Hoff DD, Rowinsky EK, Nadler P, Wood D, Hamilton M, Hage G, Wolf J and Patnaik A: Erlotinib plus gemcitabine in patients with unresectable pancreatic cancer and other solid tumors: phase IB trial. Cancer Chemother Pharmacol 60: 295-303, 2007. (Pubitemid 46742546)
18. Morgan MA, Parsels LA, Kollar LE, Normolle DP, Maybaum J and Lawrence TS: The combination of epidermal growth factor receptor inhibitors with gemcitabine and radiation in pancreatic cancer. Clin Cancer Res 14: 5142-5149, 2008.
19. Dredge K, Marriott JB, Macdonald CD, Man HW, Chen R, Muller GW, Stirling D and Dalgleish AG: Novel thalidomide analogues display anti-angiogenic activity independently of immunomodulatory effects. Br J Cancer 87: 1166-1172, 2002. (Pubitemid 35418112)
20. Gandhi AK, Kang J, Naziruddin S, Parton A, Schafer PH and Stirling DI: Lenalidomide inhibits proliferation of Namalwa CSN.70 cells and interferes with Gab1 phosphorylation and adaptor protein complex assembly. Leuk Res 30: 849-858, 2006. (Pubitemid 43816707)
21. Galustian C and Dalgleish AG: Lenalidomide: a novel anticancer drug with multiple modalities. Exp Opin Pharmacother 10: 125-133, 2009.
22. Mitsiades N, Mitsiades CS, Poulaki V, Chauhan D, Richardson PG, Hideshima T, Munshi NC, Treon SP and Anderson KC: Apoptotic signaling induced by immunomodulatory thalidomide analogs in human multiple myeloma cells: therapeutic implications. Blood 99: 4525-4530, 2002. (Pubitemid 34627223)
23. Liu WM, Nizar S and Dalgleish AG: Gemcitabine and lenalidomide combination in a patient with metastatic pancreatic cancer: a case study. Medical Oncology 27: 430-433, 2010.
24. Zhao Y, Shen S, Guo J, Chen H, Greenblatt DY, Kleeff J, Liao Q, Chen G, Friess H and Leung PS: Mitogen-activated protein kinases and chemoresistance in pancreatic cancer cells. J Surg Res 136: 325-335, 2006. (Pubitemid 44737848)
25. Chen D, Xie D, Guo S, Qiong Y, Zhimin J, Zhuofei B and Wen M: ERK signaling pathway may induce gemcitabine chemoresistance in pancreatic cancer cell line SW1990 by regulating expression of mdr-1 and RRM1 gene. Chinese-German J Clin Oncol 8: 37-41, 2009.
26. Gysin S, Lee SH, Dean NM and McMahon M: Pharmacologic inhibition of RAF→MEK→ERK signaling elicits pancreatic cancer cell cycle arrest through induced expression of p27Kip1. Cancer Res 65: 4870-4880, 2005. (Pubitemid 40740826)
27. Mahalingam D, Kelly KR, Swords RT, Carew J, Nawrocki ST and Francis J: Emerging drugs in the treatment of pancreatic cancer. Exp Opin Emerging Drugs 14: 311-328, 2009.
28. Axelson J, Lindell M, Hörlin K and Ohlsson B: Inhibition of different intracellular signal cascades in human pancreatic cancer cells. Pancreatology 5: 251-258, 2005. (Pubitemid 40754746)
29. Hirano T, Shino Y, Saito T, Komoda F, Okutomi Y, Takeda A, Ishihara T, Yamaguchi T, Saisho H and Shirasawa H: Dominant negative MEKK1 inhibits survival of pancreatic cancer cells. Oncogene 21: 5923-5928, 2002. (Pubitemid 35007243)
30. Boucher MJ, Morisset J, Vachon PH, Reed JC, Lainé J and Rivard N: MEK/ERK signaling pathway regulates the expression of Bcl-2, Bcl-X(L), and Mcl-1 and promotes survival of human apcnreatic cancer cells. J Cell Biochem 79: 355-369, 2000.
31. Galante JM, Mortenson MM, Bowles TL, Virudachalam S and Bold RJ: ERK/BCL-2 pathway in the resistance of pancreatic cancer to anoikis. J Surg Res 152: 18-25, 2009.
32. Bold RJ, Virudachalam S and McConkey DJ: BCL2 expression correlates with metastatic potential in pancreatic cancer cell lines. Cancer 92: 1122-1129, 2001. (Pubitemid 32861660)
33. Guoan X, Hanning W, Kaiyun C and Hao L: Adenovirus-mediated siRNA targeting Mcl-1 gene increases radiosensitivity of pancreatic carcinoma cells in vitro and in vivo. Surgery 147: 553-561, 2010.
34. Warr MR and Shore GC: Unique biology of Mcl-1: therapeutic opportunities in cancer. Curr Mol Med 8: 138-147, 2008. (Pubitemid 351516833)
35. Wei SH, Dong K, Lin F, Wang X, Li B, Shen JJ, Zhang Q, Wang R and Zhang HZ: Inducing apoptosis and enhancing chemosensitivity to gemcitabine via RNA interference targeting Mcl-1 gene in pancreatic carcinoma cell. Cancer Chemother Pharmacol 62: 1055-1064, 2008.
36. Shi X, Liu S, Kleef J, Friess H and Büchler MW: Acquired resistance of pancreatic cancer cells towards 5-Fluorouracil and gemctiabine is associated with altered expression of apoptosis-regulating genes. Oncology 62: 354-362, 2002. (Pubitemid 34914105)
37. Xu Z, Friess H, Solioz M, Aebi S, Korc M, Kleeff J and Büchler MW: Bcl-x(L) antisense oligonucleotides induce apoptosis and increase sensitivity of pancreatic cancer cells to gemcitabine. Int J Cancer 94: 268-274, 2001. (Pubitemid 32911423)
38. Banerjee S, Choi M, Aboukameel A, Wang Z, Mohammad M, Chen J, Yang D, Sarkar FH and Mohammad RM: Preclinical studies of apogossypolone, a novel pan inhibitor of bcl-2 and mcl-1, synergistically potentiates cytotoxic effect of gemcitabine in pancreatic cancer cells. Pancreas 39: 323-331, 2010.
39. Macoska JA, Adsule S, Tantivejkul K, Wang S, Pienta KJ and Lee CT: -(-)Gossypol promotes the apoptosis of bladder cancer cells in vitro. Pharmacol Res 58: 323-331, 2008.
40. Skoda C, Erovic BM, Wachek V, Vormittag L, Wrba F, Martinek H, Heiduschka G, Kloimstein P, Selzer E and Thurnher D: Down-regulation of Mcl-1 with antisense technology alters the effect of various cytotoxic agents used in treatment of squamous cell carcinoma of the head and neck. Oncol Rep 19: 1499-1503, 2008.
41. Chetoui N, Sylla K, Gagnon-Houde JV, Alcaide-Loridan C, Charron D, Al-Daccak R and Aoudjit F: Down-regulation of mcl-1 by small interfering RNA sensitizes resistant melanoma cells to fas-mediated apoptosis. Mol Cancer Res 6: 42-52, 2008. (Pubitemid 351378165)
42. Wang YF, Jiang CC, Kiejda KA, Gillespie S, Zhang XD and Hersey P: Apoptosis induction in human melanoma cells by inhibition of MEK is caspase-independent and mediated by the Bcl-2 family members PUMA, Bim,and Mcl-1. Clin Cancer Res 13: 4934-4942, 2007. (Pubitemid 47294802)
43. Rinehart J, Adjei AA, Lorusso PM, Waterhouse D, Hecht JR, Natale RB, Hamid O, Varterasian M, Asbury P, Kaldjian EP, Gulyas S, Mitchell DY, Herrera R, Sebolt-Leopold JS and Meyer MB: Multicenter phase II study of the oral MEK inhibitor, CI-1040, in patients with advanced non-small-cell lung, breast, colon and pancreatic cancer. J Clin Oncol 22: 4456-4462, 2004. (Pubitemid 41185111)
44. Hideshima T, Raje N, Richardson PG and Anderson KC: A review of lenalidomide in combination with dexamethasone for the treatment of multiple myeloma. Ther Clin Risk Manag 4: 129-136, 2008. (Pubitemid 351460938)
45. Pellagatti A, Jädersten M, Forsblom AM, Cattan H, Christensson B, Emanuelsson EK, Merup M, Nilsson L, Samuelsson J, Sander B, Wainscoat JS, Boultwood J and Hellström-Lindberg E: Lenalidomide inhibits the malignant clone and up-regulates the SPARC gene mapping to the commonly deleted region in 5q-syndrome patients. Proc Natl Acad Sci USA 104: 11406-11411, 2007. (Pubitemid 47175153)
46. Anderson KC: Lenalidomide and thalidomide: mechanisms of action-similarites and differences. Semin Hematol 42: S3-8, 2005.
47. Raje N, Kumar S, Hideshima T, Ishitsuka K, Chauhan D, Mitsiades C, Ppdar K, Le Gouill S, Richardson P, Munshi NC, Stirling DI, Antin JH and Anderson KC: Combination of the mTOR inhibitor rapamycin and CC-5013 has synergistic activity in multiple myeloma. Blood 104: 4188-4193, 2004. (Pubitemid 39620173)