Molecular therapeutics in pancreas cancer

World Journal of Gastrointestinal Oncology

Volumn 8, Issue 4, 2016, Pages 366-379

  Narayanan, Vignesh ^a   Weekes, Colin D ^a  

^a UNIVERSITY OF COLORADO CANCER CENTER   (United States)

Author keywords

Immunotherapy; Kirsten rat sarcoma oncogene; Pancreas neoplasm; Targeted therapy; Vaccines

Indexed keywords

ALGENPANTUCEL L; BRCA2 PROTEIN; CD40 ANTIGEN; GALGENPROSTUCEL L PLUS LITGENPROSTUCEL L; GEMCITABINE; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR VACCINE; GROWTH FACTOR RECEPTOR; IMMUNE CHECKPOINT INHIBITOR; K RAS PROTEIN; PACLITAXEL; PARTNER AND LOCALIZER OF BRCA2; SOMATOMEDIN C RECEPTOR; SONIC HEDGEHOG PROTEIN;

ADOPTIVE TRANSFER; ANGIOGENESIS; ARTICLE; CANCER STEM CELL; DESMOPLASTIC STROMA; GENE OVEREXPRESSION; GENETIC HETEROGENEITY; GENETIC REGULATION; HEDGEHOG SIGNALING; HUMAN; MOLECULAR THERAPY; MYOFIBROBLAST; NONHUMAN; PANCREATIC DUCTAL CARCINOMA; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; STELLATE CELL; STROMA; TUMOR CELL;

EID: 85018498493     PISSN: None     EISSN: 19485204     Source Type: Journal    
DOI: 10.4251/wjgo.v8.i4.366     Document Type: Article

References (125)

1. 1 Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin 2014; 64: 9-29 [PMID: 24399786 DOI: 10.3322/ caac.21208]
2. 2 Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res 2014; 74: 2913-2921 [PMID: 24840647 DOI: 10.1158/0008-5472.CAN-14-0155]
3. 3 Yeo CJ, Cameron JL, Lillemoe KD, Sitzmann JV, Hruban RH, Goodman SN, Dooley WC, Coleman J, Pitt HA. Pancreaticoduodenectomy for cancer of the head of the pancreas. 201 patients. Ann Surg 1995; 221: 721-731; discussion 731-733 [PMID:7794076 DOI: 10.1097/00000658-199506000-00011]
4. 4 Shaib Y, Davila J, Naumann C, El-Serag H. The impact of curative intent surgery on the survival of pancreatic cancer patients: a U.S. Population-based study. Am J Gastroenterol 2007; 102: 1377-1382 [PMID: 17403071 DOI: 10.1111/j.1572-0241.2007.01202.x]
5. 5 Li D, Xie K, Wolff R, Abbruzzese JL. Pancreatic cancer. Lancet 2004; 363: 1049-1057 [PMID: 15051286 DOI: 10.1016/ S0140-6736(04)15841-8]
6. 6 Burris HA, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, Cripps MC, Portenoy RK, Storniolo AM, Tarassoff P, Nelson R, Dorr FA, Stephens CD, 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 1997; 15: 2403-2413 [PMID: 9196156]
7. 7 Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, Seay T, Tjulandin SA, Ma WW, Saleh MN, Harris M, Reni M, Dowden S, Laheru D, Bahary N, Ramanathan RK, Tabernero J, Hidalgo M, Goldstein D, Van Cutsem E, Wei X, Iglesias J, Renschler MF. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 2013; 369: 1691-1703 [PMID: 24131140 DOI: 10.1056/NEJMoa1304369]
8. 8 Conroy T, Desseigne F, Ychou M, Bouché O, Guimbaud R, Bécouarn Y, Adenis A, Raoul JL, Gourgou-Bourgade S, de la Fouchardière C, Bennouna J, Bachet JB, Khemissa-Akouz F, Péré-Vergé D, Delbaldo C, Assenat E, Chauffert B, Michel P, Montoto-Grillot C, Ducreux M. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 2011; 364: 1817-1825 [PMID: 21561347 DOI: 10.1056/NEJMoa1011923]
9. 9 Hruban RH, Maitra A, Goggins M. Update on pancreatic intraepithelial neoplasia. Int J Clin Exp Pathol 2008; 1: 306-316 [PMID: 18787611]
10. 10 Feldmann G, Beaty R, Hruban RH, Maitra A. Molecular genetics of pancreatic intraepithelial neoplasia. J Hepatobiliary Pancreat Surg 2007; 14: 224-232 [PMID: 17520196 DOI: 10.1007/ s00534-006-1166-5]
11. 11 Couch FJ, Johnson MR, Rabe KG, Brune K, de Andrade M, Goggins M, Rothenmund H, Gallinger S, Klein A, Petersen GM, Hruban RH. The prevalence of BRCA2 mutations in familial pancreatic cancer. Cancer Epidemiol Biomarkers Prev 2007; 16: 342-346 [PMID: 17301269 DOI: 10.1158/1055-9965.EPI-06-0783]
12. 12 Jones S, Hruban RH, Kamiyama M, Borges M, Zhang X, Parsons DW, Lin JC, Palmisano E, Brune K, Jaffee EM, Iacobuzio-Donahue CA, Maitra A, Parmigiani G, Kern SE, Velculescu VE, Kinzler KW, Vogelstein B, Eshleman JR, Goggins M, Klein AP. Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility gene. Science 2009; 324: 217 [PMID: 19264984 DOI: 10.1126/science.1171202]
13. 13 Jones S, Zhang X, Parsons DW, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Kamiyama H, Jimeno A, Hong SM, Fu B, Lin MT, Calhoun ES, Kamiyama M, Walter K, Nikolskaya T, Nikolsky Y, Hartigan J, Smith DR, Hidalgo M, Leach SD, Klein AP, Jaffee EM, Goggins M, Maitra A, Iacobuzio-Donahue C, Eshleman JR, Kern SE, Hruban RH, Karchin R, Papadopoulos N, Parmigiani G, Vogelstein B, Velculescu VE, Kinzler KW. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science 2008; 321: 1801-1806 [PMID: 18772397 DOI: 10.1126/science.1164368]
14. 14 Witkiewicz AK, McMillan EA, Balaji U, Baek G, Lin WC, Mansour J, Mollaee M, Wagner KU, Koduru P, Yopp A, Choti MA, Yeo CJ, McCue P, White MA, Knudsen ES. Whole-exome sequencing of pancreatic cancer defines genetic diversity and therapeutic targets. Nat Commun 2015; 6: 6744 [PMID: 25855536 DOI: 10.1038/ncomms7744]
15. 15 Waddell N, Pajic M, Patch AM, Chang DK, Kassahn KS, Bailey P, Johns AL, Miller D, Nones K, Quek K, Quinn MC, Robertson AJ, Fadlullah MZ, Bruxner TJ, Christ AN, Harliwong I, Idrisoglu S, Manning S, Nourse C, Nourbakhsh E, Wani S, Wilson PJ, Markham E, Cloonan N, Anderson MJ, Fink JL, Holmes O, Kazakoff SH, Leonard C, Newell F, Poudel B, Song S, Taylor D, Waddell N, Wood S, Xu Q, Wu J, Pinese M, Cowley MJ, Lee HC, Jones MD, Nagrial AM, Humphris J, Chantrill LA, Chin V, Steinmann AM, Mawson A, Humphrey ES, Colvin EK, Chou A, Scarlett CJ, Pinho AV, Giry-Laterriere M, Rooman I, Samra JS, Kench JG, Pettitt JA, Merrett ND, Toon C, Epari K, Nguyen NQ, Barbour A, Zeps N, Jamieson NB, Graham JS, Niclou SP, Bjerkvig R, Grützmann R, Aust D, Hruban RH, Maitra A, Iacobuzio-Donahue CA, Wolfgang CL, Morgan RA, Lawlor RT, Corbo V, Bassi C, Falconi M, Zamboni G, Tortora G, Tempero MA, Gill AJ, Eshleman JR, Pilarsky C, Scarpa A, Musgrove EA, Pearson JV, Biankin AV, Grimmond SM. Whole genomes redefine the mutational landscape of pancreatic cancer. Nature 2015; 518: 495-501 [PMID: 25719666 DOI: 10.1038/nature14169]
16. 16 Bryant KL, Mancias JD, Kimmelman AC, Der CJ. KRAS: feeding pancreatic cancer proliferation. Trends Biochem Sci 2014; 39: 91-100 [PMID: 24388967 DOI: 10.1016/j.tibs.2013.12.004]
17. 17 Sousa CM, Kimmelman AC. The complex landscape of pancreatic cancer metabolism. Carcinogenesis 2014; 35: 1441-1450 [PMID: 24743516 DOI: 10.1093/carcin/bgu097]
18. 18 Stephen AG, Esposito D, Bagni RK, McCormick F. Dragging ras back in the ring. Cancer Cell 2014; 25: 272-281 [PMID: 24651010 DOI: 10.1016/j.ccr.2014.02.017]
19. 19 Van Cutsem E, van de Velde H, Karasek P, Oettle H, Vervenne WL, Szawlowski A, Schoffski P, Post S, Verslype C, Neumann H, Safran H, Humblet Y, Perez Ruixo J, Ma Y, Von Hoff D. Phase III trial of gemcitabine plus tipifarnib compared with gemcitabine plus placebo in advanced pancreatic cancer. J Clin Oncol 2004; 22: 1430-1438 [PMID: 15084616 DOI: 10.1200/JCO.2004.10.112]
20. 20 Laheru D, Shah P, Rajeshkumar NV, McAllister F, Taylor G, Goldsweig H, Le DT, Donehower R, Jimeno A, Linden S, Zhao M, Song D, Rudek MA, Hidalgo M. Integrated preclinical and clinical development of S-trans, trans-Farnesylthiosalicylic Acid (FTS, Salirasib) in pancreatic cancer. Invest New Drugs 2012; 30: 2391-2399 [PMID: 22547163 DOI: 10.1007/s10637-012-9818-6]
21. 21 Patgiri A, Yadav KK, Arora PS, Bar-Sagi D. An orthosteric inhibitor of the Ras-Sos interaction. Nat Chem Biol 2011; 7: 585-587 [PMID: 21765406 DOI: 10.1038/nchembio.612]
22. 22 Gysin S, Salt M, Young A, McCormick F. Therapeutic strategies for targeting ras proteins. Genes Cancer 2011; 2: 359-372 [PMID: 21779505 DOI: 10.1177/1947601911412376]
23. 23 Infante JR, Somer BG, Park JO, Li CP, Scheulen ME, Kasubhai SM, Oh DY, Liu Y, Redhu S, Steplewski K, Le N. A randomised, double-blind, placebo-controlled trial of trametinib, an oral MEK inhibitor, in combination with gemcitabine for patients with untreated metastatic adenocarcinoma of the pancreas. Eur J Cancer 2014; 50: 2072-2081 [PMID: 24915778 DOI: 10.1016/ j.ejca.2014.04.024]
24. 24 Bodoky G, Timcheva C, Spigel DR, La Stella PJ, Ciuleanu TE, Pover G, Tebbutt NC. A phase II open-label randomized study to assess the efficacy and safety of selumetinib (AZD6244 [ARRY-142886]) versus capecitabine in patients with advanced or metastatic pancreatic cancer who have failed first-line gemcitabine therapy. Invest New Drugs 2012; 30: 1216-1223 [PMID: 21594619 DOI: 10.1007/s10637-011-9687-4]
25. 25 Mirzoeva OK, Collisson EA, Schaefer PM, Hann B, Hom YK, Ko AH, Korn WM. Subtype-specific MEK-PI3 kinase feedback as a therapeutic target in pancreatic adenocarcinoma. Mol Cancer Ther 2013; 12: 2213-2225 [PMID: 23918833 DOI: 10.1158/1535-7163. MCT-13-0104]
26. 26 Ko AH, Tempero MA, Bekaii-Saab TB, Kuhn P, Courtin R, Ziyeh S, Tahiri S, Kelley RK, Dito E, Ong A, Linetskaya R, Mirzoeva OK, Wu CSY, Venook AP, Korn WM. Dual MEK/EGFR inhibition for advanced, chemotherapy-refractory pancreatic cancer: A multicenter phase II trial of selumetinib (AZD6244; ARRY-142886) plus erlotinib. Proceedings of the ASCO Annual Meeting 2013. J Clin Oncol 2013; 31 (suppl): abstr 4014
27. 27 Lowery MA, Kelsen DP, Stadler ZK, Yu KH, Janjigian YY, Ludwig E, D'Adamo DR, Salo-Mullen E, Robson ME, Allen PJ, Kurtz RC, O'Reilly EM. An emerging entity: pancreatic adenocarcinoma associated with a known BRCA mutation: clinical descriptors, treatment implications, and future directions. Oncologist 2011; 16: 1397-1402 [PMID: 21934105 DOI: 10.1634/ theoncologist.2011-0185]
28. 28 Jacob DA, Bahra M, Langrehr JM, Boas-Knoop S, Stefaniak R, Davis J, Schumacher G, Lippert S, Neumann UP. Combination therapy of poly (ADP-ribose) polymerase inhibitor 3-aminobenzamide and gemcitabine shows strong antitumor activity in pancreatic cancer cells. J Gastroenterol Hepatol 2007; 22: 738-748 [PMID: 17444865 DOI: 10.1111/ j.1440-1746.2006.04496.x]
29. 29 Fogelman DR, Wolff RA, Kopetz S, Javle M, Bradley C, Mok I, Cabanillas F, Abbruzzese JL. Evidence for the efficacy of Iniparib, a PARP-1 inhibitor, in BRCA2-associated pancreatic cancer. Anticancer Res 2011; 31: 1417-1420 [PMID: 21508395]
30. 30 Bendell J, O'Reilly EM, Middleton MR, Chau I, Hochster H, Fielding A, Burke W, Burris H. Phase I study of olaparib plus gemcitabine in patients with advanced solid tumours and comparison with gemcitabine alone in patients with locally advanced/metastatic pancreatic cancer. Ann Oncol 2015; 26: 804-811 [PMID: 25573533 DOI: 10.1093/annonc/mdu581]
31. 31 Lemoine NR, Hughes CM, Barton CM, Poulsom R, Jeffery RE, Klöppel G, Hall PA, Gullick WJ. The epidermal growth factor receptor in human pancreatic cancer. J Pathol 1992; 166: 7-12 [PMID: 1538276]
32. 32 Reichert M, Rustgi AK. Pancreatic ductal cells in development, regeneration, and neoplasia. J Clin Invest 2011; 121: 4572-4578 [PMID: 22133881 DOI: 10.1172/JCI57131.4572]
33. 33 Ardito CM, Grüner BM, Takeuchi KK, Lubeseder-Martellato C, Teichmann N, Mazur PK, Delgiorno KE, Carpenter ES, Halbrook CJ, Hall JC, Pal D, Briel T, Herner A, Trajkovic-Arsic M, Sipos B, Liou GY, Storz P, Murray NR, Threadgill DW, Sibilia M, Washington MK, Wilson CL, Schmid RM, Raines EW, Crawford HC, Siveke JT. EGF receptor is required for KRAS-induced pancreatic tumorigenesis. Cancer Cell 2012; 22: 304-317 [PMID: 22975374 DOI: 10.1016/j.ccr.2012.07.024]
34. 34 Navas C, Hernandez-Porras I, Schuhmacher AJ, Sibilia M, Guerra C, Barbacid M. EGF receptor signaling is essential for k-ras oncogene-driven pancreatic ductal adenocarcinoma. Cancer Cell 2012; 22: 318-330 [PMID: 22975375 DOI: 10.1016/ j.ccr.2012.08.001]
35. 35 Miyamoto Y, Maitra A, Ghosh B, Zechner U, Argani P, Iacobuzio-Donahue CA, Sriuranpong V, Iso T, Meszoely IM, Wolfe MS, Hruban RH, Ball DW, Schmid RM, Leach SD. Notch mediates TGF alpha-induced changes in epithelial differentiation during pancreatic tumorigenesis. Cancer Cell 2003; 3: 565-576 [PMID: 12842085 DOI: 10.1016/S1535-6108(03)00140-5]
36. 36 Tobita K, Kijima H, Dowaki S, Kashiwagi H, Ohtani Y, Oida Y, Yamazaki H, Nakamura M, Ueyama Y, Tanaka M, Inokuchi S, Makuuchi H. Epidermal growth factor receptor expression in human pancreatic cancer: Significance for liver metastasis. Int J Mol Med 2003; 11: 305-309 [PMID: 12579331]
37. 37 Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S, Au HJ, Murawa P, Walde D, Wolff RA, Campos D, Lim R, Ding K, Clark G, Voskoglou-Nomikos T, Ptasynski M, Parulekar W. 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 [PMID: 17452677 DOI: 10.1200/ JCO.2006.07.9525]
38. 38 Perera RM, Bardeesy N. Ready, set, go: the EGF receptor at the pancreatic cancer starting line. Cancer Cell 2012; 22: 281-282 [PMID: 22975369 DOI: 10.1016/j.ccr.2012.08.019]
39. 39 Nair PN, De Armond DT, Adamo ML, Strodel WE, Freeman JW. Aberrant expression and activation of insulin-like growth factor-1 receptor (IGF-1R) are mediated by an induction of IGF-1R promoter activity and stabilization of IGF-1R mRNA and contributes to growth factor independence and increased survival of the pancreatic cancer cell line MIA PaCa-2. Oncogene 2001; 20: 8203-8214 [PMID: 11781836 DOI: 10.1038/sj.onc.1205044]
40. 40 Kamrava M, Gius D, Casagrande G, Kohn E. Will targeting insulin growth factor help us or hurt us?: An oncologist's perspective. Ageing Res Rev 2011; 10: 62-70 [PMID: 19896561 DOI: 10.1016/j.arr.2009.10.007]
41. 41 Beltran PJ, Mitchell P, Chung YA, Cajulis E, Lu J, Belmontes B, Ho J, Tsai MM, Zhu M, Vonderfecht S, Baserga R, Kendall R, Radinsky R, Calzone FJ. AMG 479, a fully human antiinsulin-like growth factor receptor type I monoclonal antibody, inhibits the growth and survival of pancreatic carcinoma cells. Mol Cancer Ther 2009; 8: 1095-1105 [PMID: 19366899 DOI: 10.1158/1535-7163.MCT-08-1171]
42. 42 Rosen LS, Puzanov I, Friberg G, Chan E, Hwang YC, Deng H, Gilbert J, Mahalingam D, McCaffery I, Michael SA, Mita AC, Mita MM, Mulay M, Shubhakar P, Zhu M, Sarantopoulos J. Safety and pharmacokinetics of ganitumab (AMG 479) combined with sorafenib, panitumumab, erlotinib, or gemcitabine in patients with advanced solid tumors. Clin Cancer Res 2012; 18: 3414-3427 [PMID: 22510349 DOI: 10.1158/1078-0432.CCR-11-3369]
43. 43 Kindler HL, Richards DA, Garbo LE, Garon EB, Stephenson JJ, Rocha-Lima CM, Safran H, Chan D, Kocs DM, Galimi F, McGreivy J, Bray SL, Hei Y, Feigal EG, Loh E, Fuchs CS. A randomized, placebo-controlled phase 2 study of ganitumab (AMG 479) or conatumumab (AMG 655) in combination with gemcitabine in patients with metastatic pancreatic cancer. Ann Oncol 2012; 23: 2834-2842 [PMID: 22700995 DOI: 10.1093/ annonc/mds142]
44. 44 Fuchs CS, Azevedo S, Okusaka T, Van Laethem JL, Lipton LR, Riess H, Szczylik C, Moore MJ, Peeters M, Bodoky G, Ikeda M, Melichar B, Nemecek R, Ohkawa S, Swieboda-Sadlej A, Tjulandin SA, Van Cutsem E, Loberg R, Haddad V, Gansert JL, Bach BA, Carrato A. A phase 3 randomized, double-blind, placebo-controlled trial of ganitumab or placebo in combination with gemcitabine as first-line therapy for metastatic adenocarcinoma of the pancreas: the GAMMA trial. Ann Oncol 2015; 26: 921-927 [PMID: 25609246 DOI: 10.1093/annonc/mdv027]
45. 45 Subramani R, Lopez-Valdez R, Arumugam A, Nandy S, Boopalan T, Lakshmanaswamy R. Targeting insulin-like growth factor 1 receptor inhibits pancreatic cancer growth and metastasis. PLoS One 2014; 9: e97016 [PMID: 24809702 DOI: 10.1371/journal. pone.0097016]
46. 46 Feig C, Gopinathan A, Neesse A, Chan DS, Cook N, Tuveson DA. The pancreas cancer microenvironment. Clin Cancer Res 2012; 18: 4266-4276 [PMID: 22896693 DOI: 10.1158/1078-0432. CCR-11-3114]
47. 47 Mahadevan D, Von Hoff DD. Tumor-stroma interactions in pancreatic ductal adenocarcinoma. Mol Cancer Ther 2007; 6: 1186-1197 [PMID: 17406031]
48. 48 Comoglio PM, Trusolino L. Cancer: the matrix is now in control. Nat Med 2005; 11: 1156-1159 [PMID: 16270068]
49. 49 Toole BP. Hyaluronan: from extracellular glue to pericellular cue. Nat Rev Cancer 2004; 4: 528-539 [PMID: 15229478 DOI: 10.1038/nrc1391]
50. 50 Provenzano PP, Cuevas C, Chang AE, Goel VK, Von Hoff DD, Hingorani SR. Enzymatic targeting of the stroma ablates physical barriers to treatment of pancreatic ductal adenocarcinoma. Cancer Cell 2012; 21: 418-429 [PMID: 22439937 DOI: 10.1016/ j.ccr.2012.01.007]
51. 51 Hingorani SR, Harris WP, Beck JT, Berdov BA, Wagner SA, Pshevlotsky SM, Tjulandin S, Gladkov O, Holcombe RF, Jiang P, Maneval DC, Zhu J, Devoe CE. A phase 1b multi-center international study of gemcitabine combined with PEGPH20 (pegylated recombinant human hyaluronidase) in patients with stage IV previously untreated pancreatic cancer. Proceedings of the ASCO Annual Meeting 2013. J Clin Oncol 2013; 31 (suppl): abstr 4010
52. 52 Hingorani SR, Harris WP, Hendifar AE, Bullock AJ, Xionghua WW, Huang YJP. High response rate and PFS with PEGPH20 added to nab-paclitaxel/gemcitabine in stage IV previously untreated pancreatic cancer patients with high-HA tumors: Interim results of a randomized phase II study. Proceedings of the ASCO Annual Meeting 2015. J Clin Oncol 2015; 33 (suppl): abstr 4006
53. 53 Alvarez R, Musteanu M, Garcia-Garcia E, Lopez-Casas PP, Megias D, Guerra C, Muñoz M, Quijano Y, Cubillo A, Rodriguez-Pascual J, Plaza C, de Vicente E, Prados S, Tabernero S, Barbacid M, Lopez-Rios F, Hidalgo M. Stromal disrupting effects of nab-paclitaxel in pancreatic cancer. Br J Cancer 2013; 109: 926-933 [PMID: 23907428 DOI: 10.1038/bjc.2013.415]
54. 54 Von Hoff DD, Ramanathan RK, Borad MJ, Laheru DA, Smith LS, Wood TE, Korn RL, Desai N, Trieu V, Iglesias JL, Zhang H, Soon-Shiong P, Shi T, Rajeshkumar NV, Maitra A, Hidalgo M. Gemcitabine plus nab-paclitaxel is an active regimen in patients with advanced pancreatic cancer: a phase I/II trial. J Clin Oncol 2011; 29: 4548-4554 [PMID: 21969517 DOI: 10.1200/ JCO.2011.36.5742]
55. 55 Kalluri R, Zeisberg M. Fibroblasts in cancer. Nat Rev Cancer 2006; 6: 392-401 [PMID: 16572188 DOI: 10.1038/nrc1877]
56. 56 Infante JR, Matsubayashi H, Sato N, Tonascia J, Klein AP, Riall TA, Yeo C, Iacobuzio-Donahue C, Goggins M. Peritumoral fibroblast SPARC expression and patient outcome with resectable pancreatic adenocarcinoma. J Clin Oncol 2007; 25: 319-325 [PMID: 17235047 DOI: 10.1200/JCO.2006.07.8824]
57. 57 Sato N, Fukushima N, Maehara N, Matsubayashi H, Koopmann J, Su GH, Hruban RH, Goggins M. SPARC/osteonectin is a frequent target for aberrant methylation in pancreatic adenocarcinoma and a mediator of tumor-stromal interactions. Oncogene 2003; 22: 5021-5030 [PMID: 12902985 DOI: 10.1038/sj.onc.1206807]
58. 58 Nagpal S, Na S, Rathnachalam R. Noncalcemic actions of vitamin D receptor ligands. Endocr Rev 2005; 26: 662-687 [PMID: 15798098 DOI: 10.1210/er.2004-0002]
59. 59 Sherman MH, Yu RT, Engle DD, Ding N, Atkins AR, Tiriac H, Collisson EA, Connor F, Van Dyke T, Kozlov S, Martin P, Tseng TW, Dawson DW, Donahue TR, Masamune A, Shimosegawa T, Apte MV, Wilson JS, Ng B, Lau SL, Gunton JE, Wahl GM, Hunter T, Drebin JA, O'Dwyer PJ, Liddle C, Tuveson DA, Downes M, Evans RM. Vitamin D receptor-mediated stromal reprogramming suppresses pancreatitis and enhances pancreatic cancer therapy. Cell 2014; 159: 80-93 [PMID: 25259922 DOI: 10.1016/ j.cell.2014.08.007]
60. 60 Yauch RL, Gould SE, Scales SJ, Tang T, Tian H, Ahn CP, Marshall D, Fu L, Januario T, Kallop D, Nannini-Pepe M, Kotkow K, Marsters JC, Rubin LL, de Sauvage FJ. A paracrine requirement for hedgehog signalling in cancer. Nature 2008; 455: 406-410 [PMID: 18754008 DOI: 10.1038/nature07275]
61. 61 Olive KP, Jacobetz MA, Davidson CJ, Gopinathan A, McIntyre D, Honess D, Madhu B, Goldgraben MA, Caldwell ME, Allard D, Frese KK, Denicola G, Feig C, Combs C, Winter SP, Ireland-Zecchini H, Reichelt S, Howat WJ, Chang A, Dhara M, Wang L, Rückert F, Grützmann R, Pilarsky C, Izeradjene K, Hingorani SR, Huang P, Davies SE, Plunkett W, Egorin M, Hruban RH, Whitebread N, McGovern K, Adams J, Iacobuzio-Donahue C, Griffiths J, Tuveson DA. Inhibition of Hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer. Science 2009; 324: 1457-1461 [PMID: 19460966 DOI: 10.1126/science.1171362.Inhibition]
62. 62 Infinity Pharmaceuticals. Update from phase 2 study of saridegib plus gemcitabine in patients with metastatic pancreatic cancer. ID: 1653550. Available from: URL: http: //www.infi.com
63. 63 Rhim AD, Oberstein PE, Thomas DH, Mirek ET, Palermo CF, Sastra SA, Dekleva EN, Saunders T, Becerra CP, Tattersall IW, Westphalen CB, Kitajewski J, Fernandez-Barrena MG, Fernandez-Zapico ME, Iacobuzio-Donahue C, Olive KP, Stanger BZ. Stromal elements act to restrain, rather than support, pancreatic ductal adenocarcinoma. Cancer Cell 2014; 25: 735-747 [PMID: 24856585 DOI: 10.1016/j.ccr.2014.04.021]
64. 64 Özdemir BC, Pentcheva-Hoang T, Carstens JL, Zheng X, Wu CC, Simpson TR, Laklai H, Sugimoto H, Kahlert C, Novitskiy SV, De Jesus-Acosta A, Sharma P, Heidari P, Mahmood U, Chin L, Moses HL, Weaver VM, Maitra A, Allison JP, LeBleu VS, Kalluri R. Depletion of carcinoma-associated fibroblasts and fibrosis induces immunosuppression and accelerates pancreas cancer with reduced survival. Cancer Cell 2014; 25: 719-734 [PMID: 24856586 DOI: 10.1016/j.ccr.2014.04.005]
65. 65 Hanahan D, Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 1996; 86: 353-364 [PMID: 8756718]
66. 66 Itakura J, Ishiwata T, Shen B, Kornmann M, Korc M. Concomitant over-expression of vascular endothelial growth factor and its receptors in pancreatic cancer. Int J Cancer 2000; 85: 27-34 [PMID: 10585578]
67. 67 von Marschall Z, Cramer T, Höcker M, Burde R, Plath T, Schirner M, Heidenreich R, Breier G, Riecken EO, Wiedenmann B, Rosewicz S. De novo expression of vascular endothelial growth factor in human pancreatic cancer: evidence for an autocrine mitogenic loop. Gastroenterology 2000; 119: 1358-1372 [PMID: 11054395]
68. 68 Olson P, Chu GC, Perry SR, Nolan-Stevaux O, Hanahan D. Imaging guided trials of the angiogenesis inhibitor sunitinib in mouse models predict efficacy in pancreatic neuroendocrine but not ductal carcinoma. Proc Natl Acad Sci USA 2011; 108: E1275-E1284 [PMID: 22084065 DOI: 10.1073/pnas.1111079108]
69. 69 Kindler HL, Niedzwiecki D, Hollis D, Sutherland S, Schrag D, Hurwitz H, Innocenti F, Mulcahy MF, O'Reilly E, Wozniak TF, Picus J, Bhargava P, Mayer RJ, Schilsky RL, Goldberg RM. 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 [PMID: 20606091 DOI: 10.1200/ JCO.2010.28.1386]
70. 70 Van Cutsem E, Vervenne WL, Bennouna J, Humblet Y, Gill S, Van Laethem JL, Verslype C, Scheithauer W, Shang A, Cosaert J, Moore MJ. Phase III trial of bevacizumab in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer. J Clin Oncol 2009; 27: 2231-2237 [PMID: 19307500 DOI: 10.1200/JCO.2008.20.0238]
71. 71 Kindler HL, Ioka T, Richel DJ, Bennouna J, Létourneau R, Okusaka T, Funakoshi A, Furuse J, Park YS, Ohkawa S, Springett GM, Wasan HS, Trask PC, Bycott P, Ricart AD, Kim S, Van Cutsem E. Axitinib plus gemcitabine versus placebo plus gemcitabine in patients with advanced pancreatic adenocarcinoma: a double-blind randomised phase 3 study. Lancet Oncol 2011; 12: 256-262 [PMID: 21306953 DOI: 10.1016/S1470-2045(11)70004-3]
72. 72 Rougier P, Riess H, Manges R, Karasek P, Humblet Y, Barone C, Santoro A, Assadourian S, Hatteville L, Philip PA. Randomised, placebo-controlled, double-blind, parallel-group phase III study evaluating aflibercept in patients receiving first-line treatment with gemcitabine for metastatic pancreatic cancer. Eur J Cancer 2013; 49: 2633-2642 [PMID: 23642329 DOI: 10.1016/ j.ejca.2013.04.002]
73. 73 Kisker O, Onizuka S, Banyard J, Komiyama T, Becker CM, Achilles EG, Barnes CM, O'Reilly MS, Folkman J, Pirie-Shepherd SR. Generation of multiple angiogenesis inhibitors by human pancreatic cancer. Cancer Res 2001; 61: 7298-7304 [PMID: 11585769]
74. 74 Li C, Heidt DG, Dalerba P, Burant CF, Zhang L, Adsay V, Wicha M, Clarke MF, Simeone DM. Identification of pancreatic cancer stem cells. Cancer Res 2007; 67: 1030-1037 [PMID: 17283135 DOI: 10.1158/0008-5472.CAN-06-2030]
75. 75 Hermann PC, Huber SL, Herrler T, Aicher A, Ellwart JW, Guba M, Bruns CJ, Heeschen C. Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell 2007; 1: 313-323 [PMID: 18371365 DOI: 10.1016/j.stem.2007.06.002]
76. 76 Izumiya M, Kabashima A, Higuchi H, Igarashi T, Sakai G, Iizuka H, Nakamura S, Adachi M, Hamamoto Y, Funakoshi S, Takaishi H, Hibi T. Chemoresistance is associated with cancer stem cell-like properties and epithelial-to-mesenchymal transition in pancreatic cancer cells. Anticancer Res 2012; 32: 3847-3853 [PMID: 22993328]
77. 77 Du Z, Qin R, Wei C, Wang M, Shi C, Tian R, Peng C. Pancreatic cancer cells resistant to chemoradiotherapy rich in “stem-cell-like” tumor cells. Dig Dis Sci 2011; 56: 741-750 [PMID: 20683663 DOI: 10.1007/s10620-010-1340-0]
78. 78 Huang FT, Zhuan-Sun YX, Zhuang YY, Wei SL, Tang J, Chen WB, Zhang SN. Inhibition of hedgehog signaling depresses self-renewal of pancreatic cancer stem cells and reverses chemoresistance. Int J Oncol 2012; 41: 1707-1714 [PMID: 22923052 DOI: 10.3892/ ijo.2012.1597]
79. 79 Zhang GN, Liang Y, Zhou LJ, Chen SP, Chen G, Zhang TP, Kang T, Zhao YP. Combination of salinomycin and gemcitabine eliminates pancreatic cancer cells. Cancer Lett 2011; 313: 137-144 [PMID: 22030254 DOI: 10.1016/j.canlet.2011.05.030]
80. 80 Cioffi M, Dorado J, Baeuerle PA, Heeschen C. EpCAM/CD3-Bispecific T-cell engaging antibody MT110 eliminates primary human pancreatic cancer stem cells. Clin Cancer Res 2012; 18: 465-474 [PMID: 22096026 DOI: 10.1158/1078-0432. CCR-11-1270]
81. 81 Li Y, Kong D, Ahmad A, Bao B, Sarkar FH. Pancreatic cancer stem cells: emerging target for designing novel therapy. Cancer Lett 2013; 338: 94-100 [PMID: 22445908 DOI: 10.1016/ j.canlet.2012.03.018]
82. 82 Lonardo E, Hermann PC, Mueller MT, Huber S, Balic A, Miranda-Lorenzo I, Zagorac S, Alcala S, Rodriguez-Arabaolaza I, Ramirez JC, Torres-Ruiz R, Garcia E, Hidalgo M, Cebrian DA, Heuchel R, Löhr M, Berger F, Bartenstein P, Aicher A, Heeschen C. Nodal/Activin signaling drives self-renewal and tumorigenicity of pancreatic cancer stem cells and provides a target for combined drug therapy. Cell Stem Cell 2011; 9: 433-446 [PMID: 22056140 DOI: 10.1016/j.stem.2011.10.001]
83. 83 Bao B, Wang Z, Ali S, Ahmad A, Azmi AS, Sarkar SH, Banerjee S, Kong D, Li Y, Thakur S, Sarkar FH. Metformin inhibits cell proliferation, migration and invasion by attenuating CSC function mediated by deregulating miRNAs in pancreatic cancer cells. Cancer Prev Res (Phila) 2012; 5: 355-364 [PMID: 22086681 DOI: 10.1158/1940-6207.CAPR-11-0299]
84. 84 von Bernstorff W, Voss M, Freichel S, Schmid A, Vogel I, Jöhnk C, Henne-Bruns D, Kremer B, Kalthoff H. Systemic and local immunosuppression in pancreatic cancer patients. Clin Cancer Res 2001; 7: 925s-932s [PMID: 11300493]
85. 85 Clark CE, Beatty GL, Vonderheide RH. Immunosurveillance of pancreatic adenocarcinoma: insights from genetically engineered mouse models of cancer. Cancer Lett 2009; 279: 1-7 [PMID: 19013709 DOI: 10.1016/j.canlet.2008.09.037]
86. 86 Bierie B, Moses HL. Tumour microenvironment: TGFbeta: the molecular Jekyll and Hyde of cancer. Nat Rev Cancer 2006; 6: 506-520 [PMID: 16794634 DOI: 10.1038/nrc1926]
87. 87 Harizi H, Gualde N. Pivotal role of PGE2 and IL-10 in the crossregulation of dendritic cell-derived inflammatory mediators. Cell Mol Immunol 2006; 3: 271-277 [PMID: 16978535]
88. 88 Fukunaga A, Miyamoto M, Cho Y, Murakami S, Kawarada Y, Oshikiri T, Kato K, Kurokawa T, Suzuoki M, Nakakubo Y, Hiraoka K, Itoh T, Morikawa T, Okushiba S, Kondo S, Katoh H. CD8+ tumor-infiltrating lymphocytes together with CD4+ tumorinfiltrating lymphocytes and dendritic cells improve the prognosis of patients with pancreatic adenocarcinoma. Pancreas 2004; 28: e26-e31 [PMID: 14707745]
89. 89 Soares KC, Zheng L, Edil B, Jaffee EM. Vaccines for pancreatic cancer. Cancer J 2012; 18: 642-652 [PMID: 23187853 DOI: 10.1097/PPO.0b013e3182756903]
90. 90 Melief CJ, van der Burg SH. Immunotherapy of established (pre)malignant disease by synthetic long peptide vaccines. Nat Rev Cancer 2008; 8: 351-360 [PMID: 18418403 DOI: 10.1038/ nrc2373]
91. 91 Argani P, Iacobuzio-Donahue C, Ryu B, Rosty C, Goggins M, Wilentz RE, Murugesan SR, Leach SD, Jaffee E, Yeo CJ, Cameron JL, Kern SE, Hruban RH. Mesothelin is overexpressed in the vast majority of ductal adenocarcinomas of the pancreas: identification of a new pancreatic cancer marker by serial analysis of gene expression (SAGE). Clin Cancer Res 2001; 7: 3862-3868 [PMID: 11751476]
92. 92 Pastan I, Hassan R. Discovery of mesothelin and exploiting it as a target for immunotherapy. Cancer Res 2014; 74: 2907-2912 [PMID: 24824231 DOI: 10.1158/0008-5472.CAN-14-0337]
93. 93 Thomas AM, Santarsiero LM, Lutz ER, Armstrong TD, Chen YC, Huang LQ, Laheru DA, Goggins M, Hruban RH, Jaffee EM. Mesothelin-specific CD8(+) T cell responses provide evidence of in vivo cross-priming by antigen-presenting cells in vaccinated pancreatic cancer patients. J Exp Med 2004; 200: 297-306 [PMID: 15289501 DOI: 10.1084/jem.20031435]
94. 94 Jaffee EM, Hruban RH, Biedrzycki B, Laheru D, Schepers K, Sauter PR, Goemann M, Coleman J, Grochow L, Donehower RC, Lillemoe KD, O'Reilly S, Abrams RA, Pardoll DM, Cameron JL, Yeo CJ. Novel allogeneic granulocyte-macrophage colonystimulating factor-secreting tumor vaccine for pancreatic cancer: a phase I trial of safety and immune activation. J Clin Oncol 2001; 19: 145-156 [PMID: 11134207]
95. 95 Springett GM. Novel pancreatic cancer vaccines could unleash the army within. Cancer Control 2014; 21: 242-246 [PMID: 24955709]
96. 96 Lutz E, Yeo CJ, Lillemoe KD, Biedrzycki B, Kobrin B, Herman J, Sugar E, Piantadosi S, Cameron JL, Solt S, Onners B, Tartakovsky I, Choi M, Sharma R, Illei PB, Hruban RH, Abrams RA, Le D, Jaffee E, Laheru D. A lethally irradiated allogeneic granulocytemacrophage colony stimulating factor-secreting tumor vaccine for pancreatic adenocarcinoma. A Phase II trial of safety, efficacy, and immune activation. Ann Surg 2011; 253: 328-335 [PMID: 21217520 DOI: 10.1097/SLA.0b013e3181fd271c.A]
97. 97 Laheru D, Lutz E, Burke J, Biedrzycki B, Solt S, Onners B, Tartakovsky I, Nemunaitis J, Le D, Sugar E, Hege K, Jaffee E. Allogeneic granulocyte macrophage colony-stimulating factorsecreting tumor immunotherapy alone or in sequence with cyclophosphamide for metastatic pancreatic cancer: a pilot study of safety, feasibility, and immune activation. Clin Cancer Res 2008; 14: 1455-1463 [PMID: 18316569 DOI: 10.1158/1078-0432. CCR-07-0371]
98. 98 Le DT, Brockstedt DG, Nir-Paz R, Hampl J, Mathur S, Nemunaitis J, Sterman DH, Hassan R, Lutz E, Moyer B, Giedlin M, Louis JL, Sugar EA, Pons A, Cox AL, Levine J, Murphy AL, Illei P, Dubensky TW, Eiden JE, Jaffee EM, Laheru DA. A live-attenuated Listeria vaccine (ANZ-100) and a live-attenuated Listeria vaccine expressing mesothelin (CRS-207) for advanced cancers: phase I studies of safety and immune induction. Clin Cancer Res 2012; 18: 858-868 [PMID: 22147941]
99. 99 Le DT, Wang-Gillam A, Picozzi V, Greten TF, Crocenzi T, Springett G, Morse M, Zeh H, Cohen D, Fine RL, Onners B, Uram JN, Laheru DA, Lutz ER, Solt S, Murphy AL, Skoble J, Lemmens E, Grous J, Dubensky T, Brockstedt DG, Jaffee EM. Safety and survival with GVAX pancreas prime and Listeria Monocytogenesexpressing mesothelin (CRS-207) boost vaccines for metastatic pancreatic cancer. J Clin Oncol 2015; 33: 1325-1333 [PMID: 25584002 DOI: 10.1200/JCO.2014.57.4244]
100. 100 Hardacre JM, Mulcahy M, Small W, Talamonti M, Obel J, Krishnamurthi S, Rocha-Lima CS, Safran H, Lenz HJ, Chiorean EG. Addition of algenpantucel-L immunotherapy to standard adjuvant therapy for pancreatic cancer: a phase 2 study. J Gastrointest Surg 2013; 17: 94-100; discussion 100-101 [PMID: 23229886 DOI: 10.1007/s11605-012-2064-6]
101. 101 Korman AJ, Peggs KS, Allison JP. Checkpoint blockade in cancer immunotherapy. Adv Immunol 2006; 90: 297-339 [PMID: 16730267]
102. 102 Royal RE, Levy C, Turner K, Mathur A, Hughes M, Kammula US, Sherry RM, Topalian SL, Yang JC, Lowy I, Rosenberg SA. Phase 2 trial of single agent Ipilimumab (anti-CTLA-4) for locally advanced or metastatic pancreatic adenocarcinoma. J Immunother 2010; 33: 828-833 [PMID: 20842054 DOI: 10.1097/ CJI.0b013e3181eec14c]
103. 103 Le DT, Lutz E, Uram JN, Sugar EA, Onners B, Solt S, Zheng L, Diaz LA, Donehower RC, Jaffee EM, Laheru DA. Evaluation of ipilimumab in combination with allogeneic pancreatic tumor cells transfected with a GM-CSF gene in previously treated pancreatic cancer. J Immunother 2013; 36: 382-389 [PMID: 23924790 DOI: 10.1097/CJI.0b013e31829fb7a2]
104. 104 Topalian SL, Drake CG, Pardoll DM. Targeting the PD-1/B7-H1(PD-L1) pathway to activate anti-tumor immunity. Curr Opin Immunol 2012; 24: 207-212 [PMID: 22236695 DOI: 10.1016/ j.coi.2011.12.009.Targeting]
105. 105 Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, Drake CG, Camacho LH, Kauh J, Odunsi K, Pitot HC, Hamid O, Bhatia S, Martins R, Eaton K, Chen S, Salay TM, Alaparthy S, Grosso JF, Korman AJ, Parker SM, Agrawal S, Goldberg SM, Pardoll DM, Gupta A, Wigginton JM. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 2012; 366: 2455-2465 [PMID: 22658128 DOI: 10.1056/ NEJMoa1200694]
106. 106 Feig C, Jones JO, Kraman M, Wells RJ, Deonarine A, Chan DS, Connell CM, Roberts EW, Zhao Q, Caballero OL, Teichmann SA, Janowitz T, Jodrell DI, Tuveson DA, Fearon DT. Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer. Proc Natl Acad Sci USA 2013; 110: 20212-20217 [PMID: 24277834 DOI: 10.1073/pnas.1320318110]
107. 107 Wang J, Reiss KA, Khatri R, Jaffee E, Laheru D. Immune Therapy in GI Malignancies: A Review. J Clin Oncol 2015; 33: 1745-1753 [PMID: 25918295 DOI: 10.1200/JCO.2015.60.7879]
108. 108 Schoenberger SP, Toes RE, van der Voort EI, Offringa R, Melief CJ. T-cell help for cytotoxic T lymphocytes is mediated by CD40-CD40L interactions. Nature 1998; 393: 480-483 [PMID: 9624005 DOI: 10.1038/31002]
109. 109 Beatty GL, Chiorean EG, Fishman MP, Saboury B, Teitelbaum UR, Sun W, Huhn RD, Song W, Li D, Sharp LL, Torigian DA, O' Dwyer PJ, Vonderheide RH. CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans. Science 2011; 331: 1612-1616 [PMID: 21436454 DOI: 10.1126/ science.1198443]
110. 110 Beatty GL, Torigian DA, Chiorean EG, Saboury B, Brothers A, Alavi A, Troxel AB, Sun W, Teitelbaum UR, Vonderheide RH, O'Dwyer PJ. A phase I study of an agonist CD40 monoclonal antibody (CP-870,893) in combination with gemcitabine in patients with advanced pancreatic ductal adenocarcinoma. Clin Cancer Res 2013; 19: 6286-6295 [PMID: 23983255 DOI: 10.1158/1078-0432. CCR-13-1320]
111. 111 Le DT, Jaffee EM. Harnessing immune responses in the tumor microenvironment: all signals needed. Clin Cancer Res 2013; 19: 6061-6063 [PMID: 24097857 DOI: 10.1158/1078-0432. CCR-13-2424]
112. 112 Grupp SA, Kalos M, Barrett D, Aplenc R, Porter DL, Rheingold SR, Teachey DT, Chew A, Hauck B, Wright JF, Milone MC, Levine BL, June CH. Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Engl J Med 2013; 368: 1509-1518 [PMID: 23527958 DOI: 10.1056/NEJMoa1215134]
113. 113 Kalos M, June CH. Adoptive T cell transfer for cancer immunotherapy in the era of synthetic biology. Immunity 2013; 39: 49-60 [PMID: 23890063 DOI: 10.1016/j.immuni.2013.07.002]
114. 114 Beatty GL. Engineered chimeric antigen receptor-expressing T cells for the treatment of pancreatic ductal adenocarcinoma. Oncoimmunology 2014; 3: e28327 [PMID: 25050204 DOI: 10.4161/ onci.28327]
115. 115 Zhao Y, Moon E, Carpenito C, Paulos CM, Liu X, Brennan AL, Chew A, Carroll RG, Scholler J, Levine BL, Albelda SM, June CH. Multiple injections of electroporated autologous T cells expressing a chimeric antigen receptor mediate regression of human disseminated tumor. Cancer Res 2010; 70: 9053-9061 [PMID: 20926399 DOI: 10.1158/0008-5472.CAN-10-2880]
116. 116 Beatty GL, Haas AR, Maus MV, Torigian DA, Soulen MC, Plesa G, Chew A, Zhao Y, Levine BL, Albelda SM, Kalos M, June CH. Mesothelin-specific chimeric antigen receptor mRNA-engineered T cells induce anti-tumor activity in solid malignancies. Cancer Immunol Res 2014; 2: 112-120 [PMID: 24579088 DOI: 10.1158/2326-6066.CIR-13-0170]
117. 117 van Kampen JG, Marijnissen-van Zanten MA, Simmer F, van der Graaf WT, Ligtenberg MJ, Nagtegaal ID. Epigenetic targeting in pancreatic cancer. Cancer Treat Rev 2014; 40: 656-664 [PMID: 24433955 DOI: 10.1016/j.ctrv.2013.12.002]
118. 118 Schneider G, Krämer OH, Schmid RM, Saur D. Acetylation as a transcriptional control mechanism-HDACs and HATs in pancreatic ductal adenocarcinoma. J Gastrointest Cancer 2011; 42: 85-92 [PMID: 21271301 DOI: 10.1007/s12029-011-9257-1]
119. 119 Koutsounas I, Giaginis C, Theocharis S. Histone deacetylase inhibitors and pancreatic cancer: are there any promising clinical trials? World J Gastroenterol 2013; 19: 1173-1181 [PMID: 23482354 DOI: 10.3748/wjg.v19.i8.1173]
120. 120 Kozak G, Blanco FF, Brody JR. Novel Targets in Pancreatic Cancer Research. Semin Oncol 2015; 42: 177-187 [DOI: 10.1053/ j.seminoncol.2014.12.015]
121. 121 Sicard F, Gayral M, Lulka H, Buscail L, Cordelier P. Targeting miR-21 for the therapy of pancreatic cancer. Mol Ther 2013; 21: 986-994 [PMID: 23481326 DOI: 10.1038/mt.2013.35]
122. 122 du Rieu MC, Torrisani J, Selves J, Al Saati T, Souque A, Dufresne M, Tsongalis GJ, Suriawinata AA, Carrère N, Buscail L, Cordelier P. MicroRNA-21 is induced early in pancreatic ductal adenocarcinoma precursor lesions. Clin Chem 2010; 56: 603-612 [PMID: 20093556 DOI: 10.1373/clinchem.2009.137364]
123. 123 Lesina M, Kurkowski MU, Ludes K, Rose-John S, Treiber M, Klöppel G, Yoshimura A, Reindl W, Sipos B, Akira S, Schmid RM, Algül H. Stat3/Socs3 activation by IL-6 transsignaling promotes progression of pancreatic intraepithelial neoplasia and development of pancreatic cancer. Cancer Cell 2011; 19: 456-469 [PMID: 21481788 DOI: 10.1016/j.ccr.2011.03.009]
124. 124 Gilabert M, Calvo E, Airoldi A, Hamidi T, Moutardier V, Turrini O, Iovanna J. Pancreatic cancer-induced cachexia is Jak2-dependent in mice. J Cell Physiol 2014; 229: 1437-1443 [PMID: 24648112 DOI: 10.1002/jcp.24580]
125. 125 Hurwitz H, Uppal NWS. A randomized double-blind phase 2 study of ruxolitinib or placebo with capecitabine as second-line therapy in patients with metastatic pancreatic cancer. J Clin Oncol 2014; 32 (suppl): abstr 4000