Perspectives in the treatment of pancreatic adenocarcinoma

World Journal of Gastroenterology

Volumn 21, Issue 31, 2015, Pages 9297-9316

  Cid Arregui, Angel ^a   Juarez, Victoria ^b  

^a GERMAN CANCER RESEARCH CENTER DKFZ   (Germany)

^b AsteriaPharma GmbH   (Germany)

Author keywords

Adoptive T cell therapy; Antibody therapy; Biomarkers; Chemotherapy; Immune surveillance; Immunotherapy; Inhibitors; Pancreatic adenocarcinoma; Stroma; Tumor surveillance; Vaccines

Indexed keywords

BEVACIZUMAB; DURVALUMAB; ERLOTINIB; FLUOROPYRIMIDINE; FLUOROURACIL; FOLINIC ACID; GEMCITABINE; GIMERACIL PLUS OTERACIL POTASSIUM PLUS TEGAFUR; IMATINIB; IMMUNOMODULATING AGENT; IPILIMUMAB; IRINOTECAN; LIRILUMAB; MASITINIB; METALLOPROTEINASE INHIBITOR; MONOCLONAL ANTIBODY; MPDL 3280A; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE INHIBITOR; NIVOLUMAB; OLAPARIB; ONTUXIZUMAB; OXALIPLATIN; PACLITAXEL; PEMBROLIZUMAB; PIDILIZUMAB; TAREXTUMAB; TUMOR MARKER; UNINDEXED DRUG; URELUMAB; VASCULOTROPIN INHIBITOR; ANTINEOPLASTIC AGENT;

ADJUVANT CHEMORADIOTHERAPY; ADOPTIVE IMMUNOTHERAPY; ARTICLE; CANCER ADJUVANT THERAPY; CANCER COMBINATION CHEMOTHERAPY; CANCER RADIOTHERAPY; CANCER SURVIVAL; DISEASE SEVERITY; HISTOPATHOLOGY; HUMAN; IMMUNOSURVEILLANCE; IMMUNOTHERAPY; METASTASIS; PANCREAS; PANCREAS ADENOCARCINOMA; PERITONEAL CAVITY; SIGNAL TRANSDUCTION; ADJUVANT CHEMOTHERAPY; ADVERSE EFFECTS; ANIMAL; CANCER STAGING; CARCINOMA, PANCREATIC DUCTAL; IMMUNOLOGY; MOLECULARLY TARGETED THERAPY; MORTALITY; NEOADJUVANT THERAPY; PANCREAS RESECTION; PANCREATIC NEOPLASMS; PATHOLOGY; PROCEDURES; SECONDARY; TREATMENT OUTCOME;

ANIMALS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CARCINOMA, PANCREATIC DUCTAL; CHEMORADIOTHERAPY, ADJUVANT; CHEMOTHERAPY, ADJUVANT; HUMANS; IMMUNOTHERAPY; MOLECULAR TARGETED THERAPY; NEOADJUVANT THERAPY; NEOPLASM STAGING; PANCREATECTOMY; PANCREATIC NEOPLASMS; TREATMENT OUTCOME;

EID: 84940093612     PISSN: 10079327     EISSN: 22192840     Source Type: Journal    
DOI: 10.3748/wjg.v21.i31.9297     Document Type: Article

References (147)

1. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015; 136: E359-E386 [PMID: 25220842 DOI: 10.1002/ijc.29210]
2. Surveillance Research Program, NCI. SEER Stat Fact Sheets: Pancreas Cancer. Available from: URL: http://seer.cancer.gov/statfacts/html/pancreas.html 2015
3. Bockman DE. Anatomy of the Pancreas. In: Go V, DiMagno E, Gardner J, Lebenthal E, Reber H, Scheele G, editors. The Pancreas: Biology, Pathobiology, and Disease, 2nd Ed. New York: Raven Press Ltd., 1993: 1-8
4. Longnecker DS. Anatomy and Histology of the Pancreas. The Pancreapedia. Exocrine Pancreas Knowledge Base. Longnecker: Daniel, 2014
5. 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]
6. Rasheed ZA, Matsui W, Maitra A. Pathology of pancreatic stroma in PDAC. In: Grippo PJ, Munshi HG, editors. Pancreatic Cancer and Tumor Microenvironment. Trivandrum (India): Transworld Research Network, 2012
7. Neesse A, Frese KK, Bapiro TE, Nakagawa T, Sternlicht MD, Seeley TW, Pilarsky C, Jodrell DI, Spong SM, Tuveson DA. CTGF antagonism with mAb FG-3019 enhances chemotherapy response without increasing drug delivery in murine ductal pancreas cancer. Proc Natl Acad Sci USA 2013; 110: 12325-12330 [PMID: 23836645 DOI: 10.1073/pnas.1300415110]
8. Lee JJ, Perera RM, Wang H, Wu DC, Liu XS, Han S, Fitamant J, Jones PD, Ghanta KS, Kawano S, Nagle JM, Deshpande V, Boucher Y, Kato T, Chen JK, Willmann JK, Bardeesy N, Beachy PA. Stromal response to Hedgehog signaling restrains pancreatic cancer progression. Proc Natl Acad Sci USA 2014; 111: E3091-E3100 [PMID: 25024225 DOI: 10.1073/pnas.1411679111]
9. 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]
10. 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]
11. 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]
12. Kanda M, Matthaei H, Wu J, Hong SM, Yu J, Borges M, Hruban RH, Maitra A, Kinzler K, Vogelstein B, Goggins M. Presence of somatic mutations in most early-stage pancreatic intraepithelial neoplasia. Gastroenterology 2012; 142: 730-733.e9 [PMID: 22226782 DOI: 10.1053/j.gastro.2011.12.042]
13. Wu J, Matthaei H, Maitra A, Dal Molin M, Wood LD, Eshleman JR, Goggins M, Canto MI, Schulick RD, Edil BH, Wolfgang CL, Klein AP, Diaz LA, Allen PJ, Schmidt CM, Kinzler KW, Papadopoulos N, Hruban RH, Vogelstein B. Recurrent GNAS mutations define an unexpected pathway for pancreatic cyst development. Sci Transl Med 2011; 3: 92ra66 [PMID: 21775669 DOI: 10.1126/scitranslmed.3002543]
14. Fernández-Medarde A, Santos E. Ras in cancer and developmental diseases. Genes Cancer 2011; 2: 344-358 [PMID: 21779504 DOI: 10.1177/1947601911411084]
15. Kim ST, Lim do H, Jang KT, Lim T, Lee J, Choi YL, Jang HL, Yi JH, Baek KK, Park SH, Park YS, Lim HY, Kang WK, Park JO. Impact of KRAS mutations on clinical outcomes in pancreatic cancer patients treated with first-line gemcitabine-based chemotherapy. Mol Cancer Ther 2011; 10: 1993-1999 [PMID: 21862683 DOI: 10.1158/1535-7163.MCT-11-0269]
16. Eser S, Schnieke A, Schneider G, Saur D. Oncogenic KRAS signalling in pancreatic cancer. Br J Cancer 2014; 111: 817-822 [PMID: 24755884 DOI: 10.1038/bjc.2014.215]
17. 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]
18. Corcoran RB, Cheng KA, Hata AN, Faber AC, Ebi H, Coffee EM, Greninger P, Brown RD, Godfrey JT, Cohoon TJ, Song Y, Lifshits E, Hung KE, Shioda T, Dias-Santagata D, Singh A, Settleman J, Benes CH, Mino-Kenudson M, Wong KK, Engelman JA. Synthetic lethal interaction of combined BCL-XL and MEK inhibition promotes tumor regressions in KRAS mutant cancer models. Cancer Cell 2013; 23: 121-128 [PMID: 23245996 DOI: 10.1016/j.ccr.2012.11.007]
19. Ling J, Kang Y, Zhao R, Xia Q, Lee DF, Chang Z, Li J, Peng B, Fleming JB, Wang H, Liu J, Lemischka IR, Hung MC, Chiao PJ. KrasG12D-induced IKK2/β/NF-κB activation by IL-1α and p62 feedforward loops is required for development of pancreatic ductal adenocarcinoma. Cancer Cell 2012; 21: 105-120 [PMID: 22264792 DOI: 10.1016/j.ccr.2011.12.006]
20. Navas C, Hernández-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]
21. Ying H, Kimmelman AC, Lyssiotis CA, Hua S, Chu GC, Fletcher-Sananikone E, Locasale JW, Son J, Zhang H, Coloff JL, Yan H, Wang W, Chen S, Viale A, Zheng H, Paik JH, Lim C, Guimaraes AR, Martin ES, Chang J, Hezel AF, Perry SR, Hu J, Gan B, Xiao Y, Asara JM, Weissleder R, Wang YA, Chin L, Cantley LC, DePinho RA. Oncogenic Kras maintains pancreatic tumors through regulation of anabolic glucose metabolism. Cell 2012; 149: 656-670 [PMID: 22541435 DOI: 10.1016/j.cell.2012.01.058]
22. Chiche J, Brahimi-Horn MC, Pouysségur J. Tumour hypoxia induces a metabolic shift causing acidosis: a common feature in cancer. J Cell Mol Med 2010; 14: 771-794 [PMID: 20015196 DOI: 10.1111/j.1582-4934.2009.00994.x]
23. Guillaumond F, Leca J, Olivares O, Lavaut MN, Vidal N, Berthezène P, Dusetti NJ, Loncle C, Calvo E, Turrini O, Iovanna JL, Tomasini R, Vasseur S. Strengthened glycolysis under hypoxia supports tumor symbiosis and hexosamine biosynthesis in pancreatic adenocarcinoma. Proc Natl Acad Sci USA 2013; 110: 3919-3924 [PMID: 23407165 DOI: 10.1073/pnas.1219555110]
24. Son J, Lyssiotis CA, Ying H, Wang X, Hua S, Ligorio M, Perera RM, Ferrone CR, Mullarky E, Shyh-Chang N, Kang Y, Fleming JB, Bardeesy N, Asara JM, Haigis MC, DePinho RA, Cantley LC, Kimmelman AC. Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway. Nature 2013; 496: 101-105 [PMID: 23535601 DOI: 10.1038/nature12040]
25. Metallo CM, Gameiro PA, Bell EL, Mattaini KR, Yang J, Hiller K, Jewell CM, Johnson ZR, Irvine DJ, Guarente L, Kelleher JK, Vander Heiden MG, Iliopoulos O, Stephanopoulos G. Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia. Nature 2012; 481: 380-384 [PMID: 22101433 DOI: 10.1038/nature10602]
26. Wise DR, Ward PS, Shay JE, Cross JR, Gruber JJ, Sachdeva UM, Platt JM, DeMatteo RG, Simon MC, Thompson CB. Hypoxia promotes isocitrate dehydrogenase-dependent carboxylation of α-ketoglutarate to citrate to support cell growth and viability. Proc Natl Acad Sci USA 2011; 108: 19611-19616 [PMID: 22106302 DOI: 10.1073/pnas.1117773108]
27. Hustinx SR, Leoni LM, Yeo CJ, Brown PN, Goggins M, Kern SE, Hruban RH, Maitra A. Concordant loss of MTAP and p16/CDKN2A expression in pancreatic intraepithelial neoplasia: evidence of homozygous deletion in a noninvasive precursor lesion. Mod Pathol 2005; 18: 959-963 [PMID: 15832197 DOI: 10.1038/modpathol.3800377]
28. Hruban RH, Canto MI, Goggins M, Schulick R, Klein AP. Update on familial pancreatic cancer. Adv Surg 2010; 44: 293-311 [PMID: 20919528]
29. Jia J, Bosley AD, Thompson A, Hoskins JW, Cheuk A, Collins I, Parikh H, Xiao Z, Ylaya K, Dzyadyk M, Cozen W, Hernandez BY, Lynch CF, Loncarek J, Altekruse SF, Zhang L, Westlake CJ, Factor VM, Thorgeirsson S, Bamlet WR, Hewitt SM, Petersen GM, Andresson T, Amundadottir LT. CLPTM1L promotes growth and enhances aneuploidy in pancreatic cancer cells. Cancer Res 2014; 74: 2785-2795 [PMID: 24648346 DOI: 10.1158/0008-5472.CAN-13-3176]
30. Wolpin BM, Rizzato C, Kraft P, Kooperberg C, Petersen GM, Wang Z, Arslan AA, Beane-Freeman L, Bracci PM, Buring J, Canzian F, Duell EJ, Gallinger S, Giles GG, Goodman GE, Goodman PJ, Jacobs EJ, Kamineni A, Klein AP, Kolonel LN, Kulke MH, Li D, Malats N, Olson SH, Risch HA, Sesso HD, Visvanathan K, White E, Zheng W, Abnet CC, Albanes D, Andreotti G, Austin MA, Barfield R, Basso D, Berndt SI, Boutron-Ruault MC, Brotzman M, Büchler MW, Bueno-de-Mesquita HB, Bugert P, Burdette L, Campa D, Caporaso NE, Capurso G, Chung C, Cotterchio M, Costello E, Elena J, Funel N, Gaziano JM, Giese NA, Giovannucci EL, Goggins M, Gorman MJ, Gross M, Haiman CA, Hassan M, Helzlsouer KJ, Henderson BE, Holly EA, Hu N, Hunter DJ, Innocenti F, Jenab M, Kaaks R, Key TJ, Khaw KT, Klein EA, Kogevinas M, Krogh V, Kupcinskas J, Kurtz RC, LaCroix A, Landi MT, Landi S, Le Marchand L, Mambrini A, Mannisto S, Milne RL, Nakamura Y, Oberg AL, Owzar K, Patel AV, Peeters PH, Peters U, Pezzilli R, Piepoli A, Porta M, Real FX, Riboli E, Rothman N, Scarpa A, Shu XO, Silverman DT, Soucek P, Sund M, Talar-Wojnarowska R, Taylor PR, Theodoropoulos GE, Thornquist M, Tjønneland A, Tobias GS, Trichopoulos D, Vodicka P, Wactawski-Wende J, Wentzensen N, Wu C, Yu H, Yu K, Zeleniuch-Jacquotte A, Hoover R, Hartge P, Fuchs C, Chanock SJ, Stolzenberg-Solomon RS, Amundadottir LT. Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer. Nat Genet 2014; 46: 994-1000 [PMID: 25086665 DOI: 10.1038/ng.3052]
31. Vonderheide RH, Bayne LJ. Inflammatory networks and immune surveillance of pancreatic carcinoma. Curr Opin Immunol 2013; 25: 200-205 [PMID: 23422836 DOI: 10.1016/j.coi.2013.01.006]
32. Lowenfels AB, Maisonneuve P, Cavallini G, Ammann RW, Lankisch PG, Andersen JR, Dimagno EP, Andrén-Sandberg A, Domellöf L. Pancreatitis and the risk of pancreatic cancer. International Pancreatitis Study Group. N Engl J Med 1993; 328: 1433-1437 [PMID: 8479461 DOI: 10.1056/nejm199305203282001]
33. Rebours V, Boutron-Ruault MC, Schnee M, Férec C, Maire F, Hammel P, Ruszniewski P, Lévy P. Risk of pancreatic adenocarcinoma in patients with hereditary pancreatitis: a national exhaustive series. Am J Gastroenterol 2008; 103: 111-119 [PMID: 18184119 DOI: 10.1111/j.1572-0241.2007.01597.x]
34. Pylayeva-Gupta Y, Lee KE, Hajdu CH, Miller G, Bar-Sagi D. Oncogenic Kras-induced GM-CSF production promotes the development of pancreatic neoplasia. Cancer Cell 2012; 21: 836-847 [PMID: 22698407 DOI: 10.1016/j.ccr.2012.04.024]
35. De Monte L, Reni M, Tassi E, Clavenna D, Papa I, Recalde H, Braga M, Di Carlo V, Doglioni C, Protti MP. Intratumor T helper type 2 cell infiltrate correlates with cancer-associated fibroblast thymic stromal lymphopoietin production and reduced survival in pancreatic cancer. J Exp Med 2011; 208: 469-478 [PMID: 21339327 DOI: 10.1084/jem.20101876]
36. Tang Y, Xu X, Guo S, Zhang C, Tang Y, Tian Y, Ni B, Lu B, Wang H. An increased abundance of tumor-infiltrating regulatory T cells is correlated with the progression and prognosis of pancreatic ductal adenocarcinoma. PLoS One 2014; 9: e91551 [PMID: 24637664 DOI: 10.1371/journal.pone.0091551]
37. Ebrahimi B, Tucker SL, Li D, Abbruzzese JL, Kurzrock R. Cytokines in pancreatic carcinoma: correlation with phenotypic characteristics and prognosis. Cancer 2004; 101: 2727-2736 [PMID: 15526319 DOI: 10.1002/cncr.20672]
38. Corcoran RB, Contino G, Deshpande V, Tzatsos A, Conrad C, Benes CH, Levy DE, Settleman J, Engelman JA, Bardeesy N. STAT3 plays a critical role in KRAS-induced pancreatic tumorigenesis. Cancer Res 2011; 71: 5020-5029 [PMID: 21586612 DOI: 10.1158/0008-5472.CAN-11-0908]
39. 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]
40. Burger JA, Kipps TJ. CXCR4: a key receptor in the crosstalk between tumor cells and their microenvironment. Blood 2006; 107: 1761-1767 [PMID: 16269611 DOI: 10.1182/blood-2005-08-3182]
41. 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]
42. 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]
43. Koprowski H, Steplewski Z, Mitchell K, Herlyn M, Herlyn D, Fuhrer P. Colorectal carcinoma antigens detected by hybridoma antibodies. Somatic Cell Genet 1979; 5: 957-971 [PMID: 94699]
44. Kang CM, Kim JY, Choi GH, Kim KS, Choi JS, Lee WJ, Kim BR. The use of adjusted preoperative CA 19-9 to predict the recurrence of resectable pancreatic cancer. J Surg Res 2007; 140: 31-35 [PMID: 17418869 DOI: 10.1016/j.jss.2006.10.007]
45. Montgomery RC, Hoffman JP, Riley LB, Rogatko A, Ridge JA, Eisenberg BL. Prediction of recurrence and survival by post-resection CA 19-9 values in patients with adenocarcinoma of the pancreas. Ann Surg Oncol 1997; 4: 551-556 [PMID: 9367020]
46. Hartwig W, Strobel O, Hinz U, Fritz S, Hackert T, Roth C, Büchler MW, Werner J. CA19-9 in potentially resectable pancreatic cancer: perspective to adjust surgical and perioperative therapy. Ann Surg Oncol 2013; 20: 2188-2196 [PMID: 23247983 DOI: 10.1245/s10434-012-2809-1]
47. Humphris JL, Chang DK, Johns AL, Scarlett CJ, Pajic M, Jones MD, Colvin EK, Nagrial A, Chin VT, Chantrill LA, Samra JS, Gill AJ, Kench JG, Merrett ND, Das A, Musgrove EA, Sutherland RL, Biankin AV. The prognostic and predictive value of serum CA19.9 in pancreatic cancer. Ann Oncol 2012; 23: 1713-1722 [PMID: 22241899 DOI: 10.1093/annonc/mdr561]
48. Heestand GM, Murphy J, Moughan J, Regine W, Luo J, Graber M, Kunz P, Fisher G, Guha C, Lin B, Mowat R, Gaur R, Buyyounouski M, Chen Y, Chang D, Koong A. A novel biomarker panel examining response to adjuvant pancreatic cancer therapy in RTOG 9704. J Clin Oncol 2014; 32 (suppl 3): abstr 176
49. Tascilar M, Skinner HG, Rosty C, Sohn T, Wilentz RE, Offerhaus GJ, Adsay V, Abrams RA, Cameron JL, Kern SE, Yeo CJ, Hruban RH, Goggins M. The SMAD4 protein and prognosis of pancreatic ductal adenocarcinoma. Clin Cancer Res 2001; 7: 4115-4121 [PMID: 11751510]
50. Iacobuzio-Donahue CA, Fu B, Yachida S, Luo M, Abe H, Henderson CM, Vilardell F, Wang Z, Keller JW, Banerjee P, Herman JM, Cameron JL, Yeo CJ, Halushka MK, Eshleman JR, Raben M, Klein AP, Hruban RH, Hidalgo M, Laheru D. DPC4 gene status of the primary carcinoma correlates with patterns of failure in patients with pancreatic cancer. J Clin Oncol 2009; 27: 1806-1813 [PMID: 19273710 DOI: 10.1200/JCO.2008.17.7188]
51. Crane CH, Varadhachary GR, Yordy JS, Staerkel GA, Javle MM, Safran H, Haque W, Hobbs BD, Krishnan S, Fleming JB, Das P, Lee JE, Abbruzzese JL, Wolff RA. Phase II trial of cetuximab, gemcitabine, and oxaliplatin followed by chemoradiation with cetuximab for locally advanced (T4) pancreatic adenocarcinoma: correlation of Smad4(Dpc4) immunostaining with pattern of disease progression. J Clin Oncol 2011; 29: 3037-3043 [PMID: 21709185 DOI: 10.1200/jco.2010.33.8038]
52. Bachet JB, Maréchal R, Demetter P, Bonnetain F, Couvelard A, Svrcek M, Bardier-Dupas A, Hammel P, Sauvanet A, Louvet C, Paye F, Rougier P, Penna C, Vaillant JC, André T, Closset J, Salmon I, Emile JF, Van Laethem JL. Contribution of CXCR4 and SMAD4 in predicting disease progression pattern and benefit from adjuvant chemotherapy in resected pancreatic adenocarcinoma. Ann Oncol 2012; 23: 2327-2335 [PMID: 22377565 DOI: 10.1093/annonc/mdr617]
53. Poplin E, Wasan H, Rolfe L, Raponi M, Ikdahl T, Bondarenko I, Davidenko I, Bondar V, Garin A, Boeck S, Ormanns S, Heinemann V, Bassi C, Evans TR, Andersson R, Hahn H, Picozzi V, Dicker A, Mann E, Voong C, Kaur P, Isaacson J, Allen A. Randomized, multicenter, phase II study of CO-101 versus gemcitabine in patients with metastatic pancreatic ductal adenocarcinoma: including a prospective evaluation of the role of hENT1 in gemcitabine or CO-101 sensitivity. J Clin Oncol 2013; 31: 4453-4461 [PMID: 24220555 DOI: 10.1200/JCO.2013.51.0826]
54. Mayers JR, Wu C, Clish CB, Kraft P, Torrence ME, Fiske BP, Yuan C, Bao Y, Townsend MK, Tworoger SS, Davidson SM, Papagiannakopoulos T, Yang A, Dayton TL, Ogino S, Stampfer MJ, Giovannucci EL, Qian ZR, Rubinson DA, Ma J, Sesso HD, Gaziano JM, Cochrane BB, Liu S, Wactawski-Wende J, Manson JE, Pollak MN, Kimmelman AC, Souza A, Pierce K, Wang TJ, Gerszten RE, Fuchs CS, Vander Heiden MG, Wolpin BM. Elevation of circulating branched-chain amino acids is an early event in human pancreatic adenocarcinoma development. Nat Med 2014; 20: 1193-1198 [PMID: 25261994 DOI: 10.1038/nm.3686]
55. Zhou YF, Xu LX, Huang LY, Guo F, Zhang F, He XY, Yuan YZ, Yao WY. Combined detection of serum UL16-binding protein 2 and macrophage inhibitory cytokine-1 improves early diagnosis and prognostic prediction of pancreatic cancer. Oncol Lett 2014; 8: 2096-2102 [PMID: 25295097 DOI: 10.3892/ol.2014.2429]
56. Takahashi N, Fukushima T, Yorita K, Tanaka H, Chijiiwa K, Kataoka H. Dickkopf-1 is overexpressed in human pancreatic ductal adenocarcinoma cells and is involved in invasive growth. Int J Cancer 2010; 126: 1611-1620 [PMID: 19711349 DOI: 10.1002/ijc.24865]
57. Bidard FC, Huguet F, Louvet C, Mineur L, Bouché O, Chibaudel B, Artru P, Desseigne F, Bachet JB, Mathiot C, Pierga JY, Hammel P. Circulating tumor cells in locally advanced pancreatic adenocarcinoma: the ancillary CirCe 07 study to the LAP 07 trial. Ann Oncol 2013; 24: 2057-2061 [PMID: 23676420 DOI: 10.1093/annonc/mdt176]
58. Cascinu S, Falconi M, Valentini V, Jelic S. Pancreatic cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2010; 21 Suppl 5: v55-v58 [PMID: 20555103 DOI: 10.1093/annonc/mdq165]
59. Vauthey JN, Dixon E. AHPBA/SSO/SSAT Consensus Conference on Resectable and Borderline Resectable Pancreatic Cancer: rationale and overview of the conference. Ann Surg Oncol 2009; 16: 1725-1726 [PMID: 19396495 DOI: 10.1245/s10434-009-0409-5]
60. Martin RC, Scoggins CR, Egnatashvili V, Staley CA, McMasters KM, Kooby DA. Arterial and venous resection for pancreatic adenocarcinoma: operative and long-term outcomes. Arch Surg 2009; 144: 154-159 [PMID: 19221327 DOI: 10.1001/archsurg.2008.547]
61. Speer AG, Thursfield VJ, Torn-Broers Y, Jefford M. Pancreatic cancer: surgical management and outcomes after 6 years of followup. Med J Aust 2012; 196: 511-515 [PMID: 22571308]
62. Lim JE, Chien MW, Earle CC. Prognostic factors following curative resection for pancreatic adenocarcinoma: a population-based, linked database analysis of 396 patients. Ann Surg 2003; 237: 74-85 [PMID: 12496533 DOI: 10.1097/01.SLA.0000041266.10047.38]
63. Goodman MD, Saif MW. Adjuvant therapy for pancreatic cancer. JOP 2014; 15: 87-90 [PMID: 24618424]
64. Fukutomi A, Uesaka K, Boku N, Kanemoto H, Konishi M, Matsumoto I, Kaneoka Y, Shimizu Y, Nakamori S, Sakamoto H, Morinaga S, Kainuma O, Imai K, Sata N, Hishinuma S, Nakamura T, Kanai M, Hirano S, Yoshikawa Y, Ohashi Y. JASPAC 01: Randomized phase III trial of adjuvant chemotherapy with gemcitabine versus S-1 for patients with resected pancreatic cancer. J Clin Oncol 2013; 31 (suppl): abstr 4008
65. Sudo K, Nakamura K, Yamaguchi T. S-1 in the treatment of pancreatic cancer. World J Gastroenterol 2014; 20: 15110-15118 [PMID: 25386059 DOI: 10.3748/wjg.v20.i41.15110]
66. Shimada T, Yamazaki H, Guengerich FP. Ethnic-related differences in coumarin 7-hydroxylation activities catalyzed by cytochrome P4502A6 in liver microsomes of Japanese and Caucasian populations. Xenobiotica 1996; 26: 395-403 [PMID: 9173680]
67. Chuah B, Goh BC, Lee SC, Soong R, Lau F, Mulay M, Dinolfo M, Lim SE, Soo R, Furuie T, Saito K, Zergebel C, Rosen LS. Comparison of the pharmacokinetics and pharmacodynamics of S-1 between Caucasian and East Asian patients. Cancer Sci 2011; 102: 478-483 [PMID: 21143703 DOI: 10.1111/j.1349-7006.2010.01793.x]
68. ESPAC-4. European Study Group for Pancreatic Ccancer Trial 4. Combination versus single agent chemotherapy in resectable pancreatic ductal and peri-ampullary cancers. UK Clinical Research Network Study Portfolio. Available from: URL: http://public.ukcrn.org.uk/search/StudyDetail.aspx?StudyID=4307.2015
69. Berlin JD, Catalano P, Thomas JP, Kugler JW, Haller DG, Benson AB. Phase III study of gemcitabine in combination with fluorouracil versus gemcitabine alone in patients with advanced pancreatic carcinoma: Eastern Cooperative Oncology Group Trial E2297. J Clin Oncol 2002; 20: 3270-3275 [PMID: 12149301]
70. Boeck S, Hoehler T, Seipelt G, Mahlberg R, Wein A, Hochhaus A, Boeck HP, Schmid B, Kettner E, Stauch M, Lordick F, Ko Y, Geissler M, Schoppmeyer K, Kojouharoff G, Golf A, Neugebauer S, Heinemann V. Capecitabine plus oxaliplatin (CapOx) versus capecitabine plus gemcitabine (CapGem) versus gemcitabine plus oxaliplatin (mGemOx): final results of a multicenter randomized phase II trial in advanced pancreatic cancer. Ann Oncol 2008; 19: 340-347 [PMID: 17962204 DOI: 10.1093/annonc/mdm467]
71. 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, Neoptolemos JP. Phase III randomized comparison of gemcitabine versus gemcitabine plus capecitabine in patients with advanced pancreatic cancer. J Clin Oncol 2009; 27: 5513-5518 [PMID: 19858379 DOI: 10.1200/JCO.2009.24.2446]
72. Klinkenbijl JH, Jeekel J, Sahmoud T, van Pel R, Couvreur ML, Veenhof CH, Arnaud JP, Gonzalez DG, de Wit LT, Hennipman A, Wils J. Adjuvant radiotherapy and 5-fluorouracil after curative resection of cancer of the pancreas and periampullary region: phase III trial of the EORTC gastrointestinal tract cancer cooperative group. Ann Surg 1999; 230: 776-782; discussion 782-784 [PMID: 10615932]
73. Neoptolemos JP, Stocken DD, Friess H, Bassi C, Dunn JA, Hickey H, Beger H, Fernandez-Cruz L, Dervenis C, Lacaine F, Falconi M, Pederzoli P, Pap A, Spooner D, Kerr DJ, Büchler MW. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med 2004; 350: 1200-1210 [PMID: 15028824 DOI: 10.1056/NEJMoa032295]
74. Morganti AG, Falconi M, van Stiphout RG, Mattiucci GC, Alfieri S, Calvo FA, Dubois JB, Fastner G, Herman JM, Maidment BW, Miller RC, Regine WF, Reni M, Sharma NK, Ippolito E, Valentini V. Multi-institutional pooled analysis on adjuvant chemoradiation in pancreatic cancer. Int J Radiat Oncol Biol Phys 2014; 90: 911-917 [PMID: 25220717 DOI: 10.1016/j.ijrobp.2014.07.024]
75. Andriulli A, Festa V, Botteri E, Valvano MR, Koch M, Bassi C, Maisonneuve P, Sebastiano PD. Neoadjuvant/preoperative gemcitabine for patients with localized pancreatic cancer: a meta-analysis of prospective studies. Ann Surg Oncol 2012; 19: 1644-1662 [PMID: 22012027 DOI: 10.1245/s10434-011-2110-8]
76. Gillen S, Schuster T, Meyer Zum Büschenfelde C, Friess H, Kleeff J. Preoperative/neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of response and resection percentages. PLoS Med 2010; 7: e1000267 [PMID: 20422030 DOI: 10.1371/journal.pmed.1000267]
77. Tsvetkova EV, Asmis TR. Role of neoadjuvant therapy in the management of pancreatic cancer: is the era of biomarker-directed therapy here? Curr Oncol 2014; 21: e650-e657 [PMID: 25089113 DOI: 10.3747/co.21.2006]
78. Alamo JM, Marín LM, Suarez G, Bernal C, Serrano J, Barrera L, Gómez MA, Muntané J, Padillo FJ. Improving outcomes in pancreatic cancer: key points in perioperative management. World J Gastroenterol 2014; 20: 14237-14245 [PMID: 25339810 DOI: 10.3748/wjg.v20.i39.14237]
79. Heinemann V, Haas M, Boeck S. Neoadjuvant treatment of borderline resectable and non-resectable pancreatic cancer. Ann Oncol 2013; 24: 2484-2492 [PMID: 23852311 DOI: 10.1093/annonc/mdt239]
80. Katz MH, Pisters PW, Evans DB, Sun CC, Lee JE, Fleming JB, Vauthey JN, Abdalla EK, Crane CH, Wolff RA, Varadhachary GR, Hwang RF. Borderline resectable pancreatic cancer: the importance of this emerging stage of disease. J Am Coll Surg 2008; 206: 833-846; discussion 846-848 [PMID: 18471707 DOI: 10.1016/j.jamcollsurg.2007.12.020]
81. Faris JE, Blaszkowsky LS, McDermott S, Guimaraes AR, Szymonifka J, Huynh MA, Ferrone CR, Wargo JA, Allen JN, Dias LE, Kwak EL, Lillemoe KD, Thayer SP, Murphy JE, Zhu AX, Sahani DV, Wo JY, Clark JW, Fernandez-del Castillo C, Ryan DP, Hong TS. FOLFIRINOX in locally advanced pancreatic cancer: the Massachusetts General Hospital Cancer Center experience. Oncologist 2013; 18: 543-548 [PMID: 23657686 DOI: 10.1634/theoncologist.2012-0435]
82. Chauffert B, Mornex F, Bonnetain F, Rougier P, Mariette C, Bouché O, Bosset JF, Aparicio T, Mineur L, Azzedine A, Hammel P, Butel J, Stremsdoerfer N, Maingon P, Bedenne L. Phase III trial comparing intensive induction chemoradiotherapy (60 Gy, infusional 5-FU and intermittent cisplatin) followed by maintenance gemcitabine with gemcitabine alone for locally advanced unresectable pancreatic cancer. Definitive results of the 2000-01 FFCD/SFRO study. Ann Oncol 2008; 19: 1592-1599 [PMID: 18467316 DOI: 10.1093/annonc/mdn281]
83. Laurence JM, Tran PD, Morarji K, Eslick GD, Lam VW, Sandroussi C. A systematic review and meta-analysis of survival and surgical outcomes following neoadjuvant chemoradiotherapy for pancreatic cancer. J Gastrointest Surg 2011; 15: 2059-2069 [PMID: 21913045 DOI: 10.1007/s11605-011-1659-7]
84. Hammel P, Huguet F, Van Laethem J-L, Goldstein D, Glimelius B, Artru P, Borbath I, Bouche O, Shannon J, André T, Mineur L, Chibaudel B, Bonnetain F, Christophe L. Comparison of chemoradiotherapy (CRT) and chemotherapy (CT) in patients with a locally advanced pancreatic cancer (LAPC) controlled after 4 months of gemcitabine with or without erlotinib: Final results of the international phase III LAP 07 study. J Clin Onco 2013; l31 (suppl): abstr LBA4003
85. Hosein PJ, Macintyre J, Kawamura C, Maldonado JC, Ernani V, Loaiza-Bonilla A, Narayanan G, Ribeiro A, Portelance L, Merchan JR, Levi JU, Rocha-Lima CM. A retrospective study of neoadjuvant FOLFIRINOX in unresectable or borderline-resectable locally advanced pancreatic adenocarcinoma. BMC Cancer 2012; 12: 199 [PMID: 22642850 DOI: 10.1186/1471-2407-12-199]
86. 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]
87. Rocha Lima CM, Green MR, Rotche R, Miller WH, Jeffrey GM, Cisar LA, Morganti A, Orlando N, Gruia G, Miller LL. Irinotecan plus gemcitabine results in no survival advantage compared with gemcitabine monotherapy in patients with locally advanced or metastatic pancreatic cancer despite increased tumor response rate. J Clin Oncol 2004; 22: 3776-3783 [PMID: 15365074 DOI: 10.1200/jco.2004.12.082]
88. Poplin E, Feng Y, Berlin J, Rothenberg ML, Hochster H, Mitchell E, Alberts S, O'Dwyer P, Haller D, Catalano P, Cella D, Benson AB. Phase III, randomized study of gemcitabine and oxaliplatin versus gemcitabine (fixed-dose rate infusion) compared with gemcitabine (30-minute infusion) in patients with pancreatic carcinoma E6201: a trial of the Eastern Cooperative Oncology Group. J Clin Oncol 2009; 27: 3778-3785 [PMID: 19581537 DOI: 10.1200/jco.2008.20.9007]
89. 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]
90. 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]
91. Rauchwerger DR, Firby PS, Hedley DW, Moore MJ. Equilibrative-sensitive nucleoside transporter and its role in gemcitabine sensitivity. Cancer Res 2000; 60: 6075-6079 [PMID: 11085530]
92. 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]
93. Shirasaka T, Shimamato Y, Ohshimo H, Yamaguchi M, Kato T, Yonekura K, Fukushima M. Development of a novel form of an oral 5-fluorouracil derivative (S-1) directed to the potentiation of the tumor selective cytotoxicity of 5-fluorouracil by two biochemical modulators. Anticancer Drugs 1996; 7: 548-557 [PMID: 8862723]
94. Boku N, Yamamoto S, Fukuda H, Shirao K, Doi T, Sawaki A, Koizumi W, Saito H, Yamaguchi K, Takiuchi H, Nasu J, Ohtsu A. Fluorouracil versus combination of irinotecan plus cisplatin versus S-1 in metastatic gastric cancer: a randomised phase 3 study. Lancet Oncol 2009; 10: 1063-1069 [PMID: 19818685 DOI: 10.1016/s1470-2045(09)70259-1]
95. Muro K, Boku N, Shimada Y, Tsuji A, Sameshima S, Baba H, Satoh T, Denda T, Ina K, Nishina T, Yamaguchi K, Takiuchi H, Esaki T, Tokunaga S, Kuwano H, Komatsu Y, Watanabe M, Hyodo I, Morita S, Sugihara K. Irinotecan plus S-1 (IRIS) versus fluorouracil and folinic acid plus irinotecan (FOLFIRI) as second-line chemotherapy for metastatic colorectal cancer: a randomised phase 2/3 non-inferiority study (FIRIS study). Lancet Oncol 2010; 11: 853-860 [PMID: 20708966 DOI: 10.1016/s1470-2045(10)70181-9]
96. Yamada Y, Takahari D, Matsumoto H, Baba H, Nakamura M, Yoshida K, Yoshida M, Iwamoto S, Shimada K, Komatsu Y, Sasaki Y, Satoh T, Takahashi K, Mishima H, Muro K, Watanabe M, Sakata Y, Morita S, Shimada Y, Sugihara K. Leucovorin, fluorouracil, and oxaliplatin plus bevacizumab versus S-1 and oxaliplatin plus bevacizumab in patients with metastatic colorectal cancer (SOFT): an open-label, non-inferiority, randomised phase 3 trial. Lancet Oncol 2013; 14: 1278-1286 [PMID: 24225157 DOI: 10.1016/s1470-2045(13)70490-x]
97. Ueno H, Ioka T, Ikeda M, Ohkawa S, Yanagimoto H, Boku N, Fukutomi A, Sugimori K, Baba H, Yamao K, Shimamura T, Sho M, Kitano M, Cheng AL, Mizumoto K, Chen JS, Furuse J, Funakoshi A, Hatori T, Yamaguchi T, Egawa S, Sato A, Ohashi Y, Okusaka T, Tanaka M. Randomized phase III study of gemcitabine plus S-1, S-1 alone, or gemcitabine alone in patients with locally advanced and metastatic pancreatic cancer in Japan and Taiwan: GEST study. J Clin Oncol 2013; 31: 1640-1648 [PMID: 23547081 DOI: 10.1200/jco.2012.43.3680]
98. O'Reilly EM. Evolving panorama of treatment for metastatic pancreas adenocarcinoma. J Clin Oncol 2013; 31: 1621-1623 [PMID: 23547071 DOI: 10.1200/JCO.2013.48.7660]
99. Gradishar WJ, Tjulandin S, Davidson N, Shaw H, Desai N, Bhar P, Hawkins M, O'Shaughnessy J. Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oilbased paclitaxel in women with breast cancer. J Clin Oncol 2005; 23: 7794-7803 [PMID: 16172456 DOI: 10.1200/jco.2005.04.937]
100. Lobo C, Lopes G, Silva O, Gluck S. Paclitaxel albumin-bound particles (abraxane) in combination with bevacizumab with or without gemcitabine: early experience at the University of Miami/Braman Family Breast Cancer Institute. Biomed Pharmacother 2007; 61: 531-533 [PMID: 17913443 DOI: 10.1016/ j.biopha.2007.08.008]
101. Hersh EM, O'Day SJ, Ribas A, Samlowski WE, Gordon MS, Shechter DE, Clawson AA, Gonzalez R. A phase 2 clinical trial of nab-paclitaxel in previously treated and chemotherapy-naive patients with metastatic melanoma. Cancer 2010; 116: 155-163 [PMID: 19877111 DOI: 10.1002/cncr.24720]
102. Socinski MA, Manikhas GM, Stroyakovsky DL, Makhson AN, Cheporov SV, Orlov SV, Yablonsky PK, Bhar P, Iglesias J. A dose finding study of weekly and every-3-week nab-Paclitaxel followed by carboplatin as first-line therapy in patients with advanced non-small cell lung cancer. J Thorac Oncol 2010; 5: 852-861 [PMID: 20521351]
103. Frese KK, Neesse A, Cook N, Bapiro TE, Lolkema MP, Jodrell DI, Tuveson DA. nab-Paclitaxel potentiates gemcitabine activity by reducing cytidine deaminase levels in a mouse model of pancreatic cancer. Cancer Discov 2012; 2: 260-269 [PMID: 22585996 DOI: 10.1158/2159-8290.cd-11-0242]
104. Neesse A, Frese KK, Chan DS, Bapiro TE, Howat WJ, Richards FM, Ellenrieder V, Jodrell DI, Tuveson DA. SPARC independent drug delivery and antitumour effects of nab-paclitaxel in genetically engineered mice. Gut 2014; 63: 974-983 [PMID: 24067278 DOI: 10.1136/gutjnl-2013-305559]
105. 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]
106. Peddi PF, Lubner S, McWilliams R, Tan BR, Picus J, Sorscher SM, Suresh R, Lockhart AC, Wang J, Menias C, Gao F, Linehan D, Wang-Gillam A. Multi-institutional experience with FOLFIRINOX in pancreatic adenocarcinoma. JOP 2012; 13: 497-501 [PMID: 22964956 DOI: 10.6092/1590-8577/913]
107. Gunturu KS, Yao X, Cong X, Thumar JR, Hochster HS, Stein SM, Lacy J. FOLFIRINOX for locally advanced and metastatic pancreatic cancer: single institution retrospective review of efficacy and toxicity. Med Oncol 2013; 30: 361 [PMID: 23271209 DOI: 10.1007/s12032-012-0361-2]
108. Mahaseth H, Brutcher E, Kauh J, Hawk N, Kim S, Chen Z, Kooby DA, Maithel SK, Landry J, El-Rayes BF. Modified FOLFIRINOX regimen with improved safety and maintained efficacy in pancreatic adenocarcinoma. Pancreas 2013; 42: 1311-1315 [PMID: 24152956 DOI: 10.1097/MPA.0b013e31829e2006]
109. Gill S, Ho MI, Kennecke HF, Renouf DJ, Cheung WI, Lim HJ. Defining eligibility of FOLFIRINOX for first-line metastatic pancreatic adenocarcinoma (MPC) in the province of British Columbia: A population-based retrospective study. Proceedings of the ASCO: Annual Meeting, 2012
110. Bryant HE, Schultz N, Thomas HD, Parker KM, Flower D, Lopez E, Kyle S, Meuth M, Curtin NJ, Helleday T. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature 2005; 434: 913-917 [PMID: 15829966 DOI: 10.1038/nature03443]
111. Kaufman B, Shapira-Frommer R, Schmutzler RK, Audeh MW, Friedlander M, Balmaña J, Mitchell G, Fried G, Stemmer SM, Hubert A, Rosengarten O, Steiner M, Loman N, Bowen K, Fielding A, Domchek SM. Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J Clin Oncol 2015; 33: 244-250 [PMID: 25366685 DOI: 10.1200/JCO.2014.56.2728]
112. Bramhall SR, Rosemurgy A, Brown PD, Bowry C, Buckels JA; Marimastat Pancreatic Cancer Study Group. Marimastat as firstline therapy for patients with unresectable pancreatic cancer: a randomized trial. J Clin Oncol 2001; 19: 3447-3455 [PMID: 11481349]
113. Bramhall SR, Schulz J, Nemunaitis J, Brown PD, Baillet M, Buckels JA. 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 [PMID: 12107836 DOI: 10.1038/sj.bjc.6600446]
114. Niedergethmann M, Hildenbrand R, Wostbrock B, Hartel M, Sturm JW, Richter A, Post S. High expression of vascular endothelial growth factor predicts early recurrence and poor prognosis after curative resection for ductal adenocarcinoma of the pancreas. Pancreas 2002; 25: 122-129 [PMID: 12142733]
115. Seo Y, Baba H, Fukuda T, Takashima M, Sugimachi K. High expression of vascular endothelial growth factor is associated with liver metastasis and a poor prognosis for patients with ductal pancreatic adenocarcinoma. Cancer 2000; 88: 2239-2245 [PMID: 10820344]
116. Spano JP, Chodkiewicz C, Maurel J, Wong R, Wasan H, Barone C, Létourneau R, Bajetta E, Pithavala Y, Bycott P, Trask P, Liau K, Ricart AD, Kim S, Rixe O. Efficacy of gemcitabine plus axitinib compared with gemcitabine alone in patients with advanced pancreatic cancer: an open-label randomised phase II study. Lancet 2008; 371: 2101-2108 [PMID: 18514303 DOI: 10.1016/S0140-6736(08)60661-3]
117. 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]
118. 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]
119. Madden JI. Infinity Reports Update from Phase 2 Study of Saridegib Plus Gemcitabine in Patients with Metastatic Pancreatic Cancer. Available from: URL: http://phx.corporate-ir.net/phoenix. zhtml?c=121941&p=irol-newsArticle&ID=1653550&highlight=.2012
120. Catenacci DVT, Bahary N, Nattam SR, Marsh RW, Wallace JA, Rajdev L, Cohen DJ, Sleckman BG, Lenz HJ, Stiff PJ, Thomas SP, Xu P, Henderson L, Horiba MN, Vannier M, Karrison T, W.M. S, Kindler HL. Final analysis of a phase IB/randomized phase II study of gemcitabine (G) plus placebo (P) or vismodegib (V), a hedgehog (Hh) pathway inhibitor, in patients (pts) with metastatic pancreatic cancer (PC): A University of Chicago phase II consortium study. J Clin Oncol 2013; 31: abstr 4012
121. Mitry E, Hammel P, Deplanque G, Mornex F, Levy P, Seitz JF, Moussy A, Kinet JP, Hermine O, Rougier P, Raymond E. Safety and activity of masitinib in combination with gemcitabine in patients with advanced pancreatic cancer. Cancer Chemother Pharmacol 2010; 66: 395-403 [PMID: 20364428 DOI: 10.1007/s00280-010-1299-8]
122. Scott AM, Wolchok JD, Old LJ. Antibody therapy of cancer. Nat Rev Cancer 2012; 12: 278-287 [PMID: 22437872 DOI: 10.1038/nrc3236]
123. Chen L, Flies DB. Molecular mechanisms of T cell co-stimulation and co-inhibition. Nat Rev Immunol 2013; 13: 227-242 [PMID: 23470321 DOI: 10.1038/nri3405]
124. Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 2012; 12: 252-264 [PMID: 22437870 DOI: 10.1038/nrc3239]
125. Postow MA, Callahan MK, Wolchok JD. Immune Checkpoint Blockade in Cancer Therapy. J Clin Oncol 2015; 33: 1974-1982 [PMID: 25605845 DOI: 10.1200/JCO.2014.59.4358]
126. Page DB, Postow MA, Callahan MK, Allison JP, Wolchok JD. Immune modulation in cancer with antibodies. Annu Rev Med 2014; 65: 185-202 [PMID: 24188664 DOI: 10.1146/annurevmed-092012-112807]
127. Powles T, Eder JP, Fine GD, Braiteh FS, Loriot Y, Cruz C, Bellmunt J, Burris HA, Petrylak DP, Teng SL, Shen X, Boyd Z, Hegde PS, Chen DS, Vogelzang NJ. MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature 2014; 515: 558-562 [PMID: 25428503 DOI: 10.1038/nature13904]
128. Tumeh PC, Harview CL, Yearley JH, Shintaku IP, Taylor EJ, Robert L, Chmielowski B, Spasic M, Henry G, Ciobanu V, West AN, Carmona M, Kivork C, Seja E, Cherry G, Gutierrez AJ, Grogan TR, Mateus C, Tomasic G, Glaspy JA, Emerson RO, Robins H, Pierce RH, Elashoff DA, Robert C, Ribas A. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature 2014; 515: 568-571 [PMID: 25428505 DOI: 10.1038/nature13954]
129. Vinay DS, Kwon BS. Immunotherapy of cancer with 4-1BB. Mol Cancer Ther 2012; 11: 1062-1070 [PMID: 22532596 DOI: 10.1158/1535-7163.MCT-11-0677]
130. Philip PA, Benedetti J, Corless CL, Wong R, O'Reilly EM, Flynn PJ, Rowland KM, Atkins JN, Mirtsching BC, Rivkin SE, Khorana AA, Goldman B, Fenoglio-Preiser CM, Abbruzzese JL, Blanke CD. Phase III study comparing gemcitabine plus cetuximab versus gemcitabine in patients with advanced pancreatic adenocarcinoma: Southwest Oncology Group-directed intergroup trial S0205. J Clin Oncol 2010; 28: 3605-3610 [PMID: 20606093 DOI: 10.1200/ JCO.2009.25.7550]
131. Fensterer H, Schade-Brittinger C, Müller HH, Tebbe S, Fass J, Lindig U, Settmacher U, Schmidt WE, Märten A, Ebert MP, Kornmann M, Hofheinz R, Endlicher E, Brendel C, Barth PJ, Bartsch DK, Michl P, Gress TM. Multicenter phase II trial to investigate safety and efficacy of gemcitabine combined with cetuximab as adjuvant therapy in pancreatic cancer (ATIP). Ann Oncol 2013; 24: 2576-2581 [PMID: 23897705 DOI: 10.1093/annonc/mdt270]
132. Kindler HL, Friberg G, Singh DA, Locker G, Nattam S, Kozloff M, Taber DA, Karrison T, Dachman A, Stadler WM, Vokes EE. Phase II trial of bevacizumab plus gemcitabine in patients with advanced pancreatic cancer. J Clin Oncol 2005; 23: 8033-8040 [PMID: 16258101 DOI: 10.1200/JCO.2005.01.9661]
133. Hoshi H, Sawada T, Uchida M, Iijima H, Kimura K, Hirakawa K, Wanibuchi H. MUC5AC protects pancreatic cancer cells from TRAIL-induced death pathways. Int J Oncol 2013; 42: 887-893 [PMID: 23292004 DOI: 10.3892/ijo.2013.1760]
134. Nath S, Daneshvar K, Roy LD, Grover P, Kidiyoor A, Mosley L, Sahraei M, Mukherjee P. MUC1 induces drug resistance in pancreatic cancer cells via upregulation of multidrug resistance genes. Oncogenesis 2013; 2: e51 [PMID: 23774063 DOI: 10.1038/oncsis.2013.16]
135. 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]
136. 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]
137. 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]
138. Gilliam AD, Broome P, Topuzov EG, Garin AM, Pulay I, Humphreys J, Whitehead A, Takhar A, Rowlands BJ, Beckingham IJ. An international multicenter randomized controlled trial of G17DT in patients with pancreatic cancer. Pancreas 2012; 41: 374-379 [PMID: 22228104 DOI: 10.1097/MPA.0b013e31822ade7e]
139. Rocha-Lima CM, de Queiroz Marques Junior E, Bayraktar S, Broome P, Weissman C, Nowacki M, Leslie M, Susnerwala S. A multicenter phase II study of G17DT immunogen plus irinotecan in pretreated metastatic colorectal cancer progressing on irinotecan. Cancer Chemother Pharmacol 2014; 74: 479-486 [PMID: 25030089 DOI: 10.1007/s00280-014-2520-y]
140. Abou-Alfa GK, Chapman PB, Feilchenfeldt J, Brennan MF, Capanu M, Gansukh B, Jacobs G, Levin A, Neville D, Kelsen DP, O'Reilly EM. Targeting mutated K-ras in pancreatic adenocarcinoma using an adjuvant vaccine. Am J Clin Oncol 2011; 34: 321-325 [PMID: 20686403 DOI: 10.1097/COC.0b013e3181e84b1f]
141. Yutani S, Komatsu N, Yoshitomi M, Matsueda S, Yonemoto K, Mine T, Noguchi M, Ishihara Y, Yamada A, Itoh K, Sasada T. A phase II study of a personalized peptide vaccination for chemotherapy-resistant advanced pancreatic cancer patients. Oncol Rep 2013; 30: 1094-1100 [PMID: 23784011 DOI: 10.3892/or.2013.2556]
142. Robbins PF, Kassim SH, Tran TL, Crystal JS, Morgan RA, Feldman SA, Yang JC, Dudley ME, Wunderlich JR, Sherry RM, Kammula US, Hughes MS, Restifo NP, Raffeld M, Lee CC, Li YF, El-Gamil M, Rosenberg SA. A pilot trial using lymphocytes genetically engineered with an NY-ESO-1-reactive T-cell receptor: long-term follow-up and correlates with response. Clin Cancer Res 2015; 21: 1019-1027 [PMID: 25538264 DOI: 10.1158/1078-0432.ccr-14-2708]
143. Kershaw MH, Westwood JA, Darcy PK. Gene-engineered T cells for cancer therapy. Nat Rev Cancer 2013; 13: 525-541 [PMID: 23880905 DOI: 10.1038/nrc3565]
144. Slaney CY, Kershaw MH, Darcy PK. Trafficking of T cells into tumors. Cancer Res 2014; 74: 7168-7174 [PMID: 25477332 DOI: 10.1158/0008-5472.can-14-2458]
145. Oettle H, Neuhaus P, Hochhaus A, Hartmann JT, Gellert K, Ridwelski K, Niedergethmann M, Zülke C, Fahlke J, Arning MB, Sinn M, Hinke A, Riess H. Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. JAMA 2013; 310: 1473-1481 [PMID: 24104372 DOI: 10.1001/jama.2013.279201]
146. Neoptolemos JP, Stocken DD, Bassi C, Ghaneh P, Cunningham D, Goldstein D, Padbury R, Moore MJ, Gallinger S, Mariette C, Wente MN, Izbicki JR, Friess H, Lerch MM, Dervenis C, Oláh A, Butturini G, Doi R, Lind PA, Smith D, Valle JW, Palmer DH, Buckels JA, Thompson J, McKay CJ, Rawcliffe CL, Büchler MW. Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial. JAMA 2010; 304: 1073-1081 [PMID: 20823433 DOI: 10.1001/jama.2010.1275]
147. Regine WF, Winter KA, Abrams R, Safran H, Hoffman JP, Konski A, Benson AB, Macdonald JS, Rich TA, Willett CG. Fluorouracil-based chemoradiation with either gemcitabine or fluorouracil chemotherapy after resection of pancreatic adenocarcinoma: 5-year analysis of the U.S. Intergroup/RTOG 9704 phase III trial. Ann Surg Oncol 2011; 18: 1319-1326 [PMID: 21499862 DOI: 10.1245/s10434-011-1630-6]