A. Jemal, R. Siegel, E. Ward, Y. Hao, J. Xu et al., Cancer Statistics, 2009, Cancer statistics, pp.225-274, 2009.
DOI : 10.3322/caac.20006

J. Klapman and M. Malafa, Early detection of pancreatic cancer: why, who, and how to screen, Cancer Control, vol.15, pp.280-287, 2008.

J. Helm, B. Centeno, D. Coppola, M. Druta, J. Park et al., Outcomes following resection of pancreatic adenocarcinoma: 20-year experience at a single institution, Cancer Control, vol.15, pp.288-94, 2008.

T. Cartwright, D. Richards, and K. Boehm, Cancer of the pancreas: are we making progress? A review of studies in the US Oncology Research Network, Cancer Control, vol.15, pp.308-321, 2008.

J. Nieto, M. Grossbard, and P. Kozuch, Metastatic Pancreatic Cancer 2008: Is the Glass Less Empty?, The Oncologist, vol.13, issue.5, pp.562-76, 2008.
DOI : 10.1634/theoncologist.2007-0181

V. Heinemann, P. Philip, and U. Pelzer, Accomplishments in 2008 in the treatment of metastatic pancreatic cancer, Gastrointest Cancer Res, vol.3, pp.43-50, 2009.

M. Moore, D. Goldstein, J. Hamm, A. Figer, J. Hecht et al., Erlotinib Plus Gemcitabine Compared With Gemcitabine Alone in Patients With Advanced Pancreatic Cancer: A Phase III Trial of the National Cancer Institute of Canada Clinical Trials Group, Journal of Clinical Oncology, vol.25, issue.15, pp.1960-1966, 2007.
DOI : 10.1200/JCO.2006.07.9525

. Erlotinib, S. Morrison, M. Clarke, and I. Weissman, line treatment of locally advanced or metastatic adenocarcinoma of the pancreasWilliston Park) Stem cells, cancer, and cancer stem cells, Oncology Nature, vol.219414, issue.712, pp.1696-706105, 2001.

J. Visvader and G. Lindeman, Cancer stem cells in solid tumours: accumulating evidence and unresolved questions, Nature Reviews Cancer, vol.63, issue.10, pp.755-68, 2008.
DOI : 10.1158/0008-5472.CAN-06-3126

C. Li, D. Heidt, P. Dalerba, C. Burant, L. Zhang et al., Identification of Pancreatic Cancer Stem Cells, Cancer Research, vol.67, issue.3, pp.1030-1037, 2007.
DOI : 10.1158/0008-5472.CAN-06-2030

D. Simeone, Pancreatic Cancer Stem Cells: Implications for the Treatment of Pancreatic Cancer, Clinical Cancer Research, vol.14, issue.18, pp.5646-5654, 2008.
DOI : 10.1158/1078-0432.CCR-08-0584

R. Hwang, T. Moore, T. Arumugam, V. Ramachandran, K. Amos et al., Cancerassociated stromal fibroblasts promote pancreatic tumor progression Hernandez-Munoz I, Skoudy A, Real FX, Navarro P. Pancreatic ductal adenocarcinoma: cellular origin, signaling pathways and stroma contribution, Cancer Res. Pancreatology, vol.688, issue.15, pp.918-26462, 2008.

M. Saif, N. Podoltsev, M. Rubin, J. Figueroa, M. Lee et al., Phase II clinical trial of paclitaxel loaded polymeric micelle in patients with advanced pancreatic cancer Therapeutic antibodies: successes, limitations and hopes for the future, Cancer Invest. Br J Pharmacol. Curr Opin Drug Discov Devel, vol.2815712, issue.17, pp.186-94220, 2009.

P. Chames and D. Baty, Bispecific antibodies for cancer therapy, mAbs, vol.47, issue.6, pp.539-586, 2009.
DOI : 10.1158/1078-0432.CCR-07-1488

URL : https://hal.archives-ouvertes.fr/inserm-00448211

K. Xie, D. Wei, and S. Huang, Transcriptional anti-angiogenesis therapy of human pancreatic cancer, Cytokine & Growth Factor Reviews, vol.17, issue.3
DOI : 10.1016/j.cytogfr.2006.01.002

J. Tabernero, The Role of VEGF and EGFR Inhibition: Implications for Combining Anti-VEGF and Anti-EGFR Agents, Molecular Cancer Research, vol.5, issue.3, pp.203-223, 2007.
DOI : 10.1158/1541-7786.MCR-06-0404

M. Niedergethmann, R. Hildenbrand, B. Wostbrock, M. Hartel, J. Sturm et al., High Expression of Vascular Endothelial Growth Factor Predicts Early Recurrence and Poor Prognosis after Curative Resection for Ductal Adenocarcinoma of the Pancreas, Pancreas, vol.25, issue.2, pp.122-131, 2002.
DOI : 10.1097/00006676-200208000-00002

S. Holloway, A. Beck, L. Shivakumar, J. Shih, J. Fleming et al., Selective Blockade of Vascular Endothelial Growth Factor Receptor 2 With an Antibody Against Tumor-Derived Vascular Endothelial Growth Factor Controls the Growth of Human Pancreatic Adenocarcinoma Xenografts, Annals of Surgical Oncology, vol.54, issue.Suppl 4, pp.1145-55, 2006.
DOI : 10.1245/ASO.2006.05.049

H. Kindler, G. Friberg, D. Singh, G. Locker, S. Nattam et al., Phase II trial of bevacizumab plus gemcitabine in patients with advanced pancreatic cancer A double-blind, placebo-controlled, randomized phase III trial of gemcitabine (G) plus bevacizumab (B) versus gemcitabine plus placebo (P) in patients (pts) with advanced pancreatic cancer (PC): A preliminary analysis of Cancer and Leukemia Group B (CALGB) Phase III trial of bevacizumab in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer, M, et al. Volociximab, a chimeric monoclonal antibody that specifically binds alpha5beta1 integrin: a phase I, pharmacokinetic, and biological correlative study, pp.8033-402231, 2005.

V. Ramakrishnan, V. Bhaskar, D. Law, M. Wong, R. Dubridge et al., Preclinical evaluation of an anti-alpha5beta1 integrin antibody as a novel anti-angiogenic agent, J Exp Ther Oncol, vol.5, pp.273-86, 2006.

M. Fjallskog, M. Lejonklou, K. Oberg, B. Eriksson, and E. Janson, Expression of molecular targets for tyrosine kinase receptor antagonists in malignant endocrine pancreatic tumors, Clin Cancer Res, vol.9, pp.1469-73, 2003.

K. Tobita, H. Kijima, S. Dowaki, H. Kashiwagi, Y. Ohtani et al., Epidermal growth factor receptor expression in human pancreatic cancer: Significance for liver metastasis, International Journal of Molecular Medicine, vol.11, pp.305-314, 2003.
DOI : 10.3892/ijmm.11.3.305

H. Xiong, A. Rosenberg, A. Lobuglio, W. Schmidt, R. Wolff et al., Cetuximab, a Monoclonal Antibody Targeting the Epidermal Growth Factor Receptor, in Combination With Gemcitabine for Advanced Pancreatic Cancer: A Multicenter Phase II Trial, Journal of Clinical Oncology, vol.22, issue.13, pp.2610-2616, 2004.
DOI : 10.1200/JCO.2004.12.040

P. Philips, J. Benedetti, C. Fenoglio-preiser, M. Zalupski, H. Lenz et al., Phase III study of gemcitabine [G] plus cetuximab [C] versus gemcitabine in patients [pts] with locally advanced or metastatic pancreatic adenocarcinoma [PC]: SWOG S0205 study Phase II ECOG trial of irinotecan/docetaxel with or without cetuximab in metastatic pancreatic cancer: Updated survival and CA19?9 results, J Clin Oncol. J Clin Oncol. Br J Cancer, vol.252694, pp.1293-1302, 2006.

X. Yang, X. Jia, J. Corvalan, P. Wang, C. Davis et al., Eradication of established tumors by a fully human monoclonal antibody to the epidermal growth factor receptor without concomitant chemotherapy, Cancer Res, vol.59, pp.1236-1279, 1999.

H. Safran, M. Steinhoff, S. Mangray, R. Rathore, T. King et al., Overexpression of the HER-2/neu oncogene in pancreatic adenocarcinoma Trastuzumab: A review of its use as adjuvant treatment in human epidermal growth factor receptor 2 (HER2)-positive early breast cancer, Am J Clin Oncol. Drugs, vol.2470, issue.37, pp.496-9215, 2001.

H. Safran, D. Iannitti, R. Ramanathan, J. Schwartz, M. Steinhoff et al., Herceptin and gemcitabine for metastatic pancreatic cancers that overexpress HER-2/neu A prospective, nonrandomized phase II trial of Trastuzumab and Capecitabine in patients with HER2 expressing metastasized pancreatic cancer Combined cetuximab and trastuzumab are superior to gemcitabine in the treatment of human pancreatic carcinoma xenografts, Cancer Invest. BMC Surg. Ann Oncol, vol.22921, issue.39, pp.706-1298, 2004.

K. Chang, I. Pastan, R. Hassan, and M. Ho, Molecular cloning of mesothelin, a differentiation antigen present on mesothelium, mesotheliomas, and ovarian cancers Mesothelin targeted cancer immunotherapy, Proc Natl Acad Sci U S A. Eur J Cancer, vol.9344, issue.42, pp.136-4046, 1996.

P. Argani, C. Iacobuzio-donahue, B. Ryu, C. Rosty, M. Goggins et al., 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, vol.7, pp.3862-3870, 2001.

R. Hassan, Z. Laszik, M. Lerner, M. Raffeld, R. Postier et al., Mesothelin Is Overexpressed in Pancreaticobiliary Adenocarcinomas but Not in Normal Pancreas and Chronic Pancreatitis, American Journal of Clinical Pathology, vol.124, issue.6, pp.838-883, 2005.
DOI : 10.1309/F1B64CL7H8VJKEAF

R. Hassan, T. Bera, and I. Pastan, Mesothelin: A New Target for Immunotherapy, Clinical Cancer Research, vol.10, issue.12, pp.3937-3979, 2004.
DOI : 10.1158/1078-0432.CCR-03-0801

R. Hassan, S. Bullock, A. Premkumar, R. Kreitman, H. Kindler et al., Phase I Study of SS1P, a Recombinant Anti-Mesothelin Immunotoxin Given as a Bolus I.V. Infusion to Patients with Mesothelin-Expressing Mesothelioma, Ovarian, and Pancreatic Cancers, Clinical Cancer Research, vol.13, issue.17, pp.5144-5153, 2007.
DOI : 10.1158/1078-0432.CCR-07-0869

R. Hassan, W. Ebel, E. Routhier, R. Patel, J. Kline et al., Preclinical evaluation of MORAb-009, a chimeric antibody targeting tumor-associated mesothelin A phase I study of MORab-009, a monoclonal antibody against mesothelin, in mesothelioma, pancreatic and ovarian cancer, Cancer Immun. J Clin Oncol, vol.726, pp.20-49, 2007.

K. Yamaguchi, M. Enjoji, and M. Tsuneyoshi, Pancreatoduodenal carcinoma: A clinicopathologic study of 304 patients and immunohistochemical observation for CEA and CA19-9, Journal of Surgical Oncology, vol.55, issue.3, pp.148-54, 1991.
DOI : 10.1002/jso.2930470303

R. Blumenthal, H. Hansen, D. Goldenberg, S. Shore, M. Raraty et al., NCA-90) and CEACAM5 (Carcinoembryonic Antigen) Randomised Phase I/II trial assessing the safety and efficacy of radiolabelled anti-carcinoembryonic antigen I(131) KAb201 antibodies given intra-arterially or intravenously in patients with unresectable pancreatic adenocarcinoma IMC-A12, a human IgG1 monoclonal antibody to the insulin-like growth factor I receptor al. A fully human monoclonal antibody to the insulin-like growth factor I receptor blocks ligand-dependent signaling and inhibits human tumor growth in vivo, Cancer Res. BMC Cancer. Clin Cancer Res. Cancer Res, vol.6591363, issue.54, pp.8809-1766, 2003.

P. Beltran, P. Mitchell, Y. Chung, E. Cajulis, J. Lu et al., AMG 479, a fully human anti-insulin-like growth factor receptor type I monoclonal antibody, inhibits the growth and survival of pancreatic carcinoma cells Extracellular N-domain alone can mediate specific heterophilic adhesion between members of the carcinoembryonic antigen family, Biochem Biophys Res Commun, vol.278, pp.6-8564, 2000.

H. Han, D. Bearss, L. Browne, R. Calaluce, R. Nagle et al., Identification of differentially expressed genes in pancreatic cancer cells using cDNA microarray, Cancer Res, vol.62, pp.2890-2896, 2002.

B. Ryu, J. Jones, N. Blades, G. Parmigiani, M. Hollingsworth et al., Relationships and differentially expressed genes among pancreatic cancers examined by large-scale serial analysis of gene expression Highly expressed genes in pancreatic ductal adenocarcinomas: a comprehensive characterization and comparison of the transcription profiles obtained from three major technologies al. Exploration of global gene expression patterns in pancreatic adenocarcinoma using cDNA microarrays, Cancer Res. Cancer Res. Am J Pathol, vol.6263162, issue.61, pp.819-268614, 2002.

L. Strickland, R. J. Williams, S. Ross, S. Romero, M. Spencer et al., Preclinical evaluation of carcinoembryonic cell adhesion molecule (CEACAM) 6 as potential therapy target for pancreatic adenocarcinoma, The Journal of Pathology, vol.125, issue.3, pp.380-90, 2009.
DOI : 10.1002/path.2545

C. Riley, K. Engelhardt, J. Saldanha, W. Qi, L. Cooke et al., Design and Activity of a Murine and Humanized Anti-CEACAM6 Single-Chain Variable Fragment in the Treatment of Pancreatic Cancer, Cancer Research, vol.69, issue.5, pp.1933-1973, 2009.
DOI : 10.1158/0008-5472.CAN-08-2707

C. Ordonez, R. Screaton, C. Ilantzis, and C. Stanners, Human carcinoembryonic antigen functions as a general inhibitor of anoikis, Cancer Res, vol.60, pp.3419-3443, 2000.

P. Baeuerle and O. Gires, EpCAM (CD326) finding its role in cancer, British Journal of Cancer, vol.15, issue.3, pp.417-440, 2007.
DOI : 10.1016/j.jim.2005.03.006

O. Gires, C. Klein, P. Baeuerle, D. Maetzel, S. Denzel et al., On the abundance of EpCAM on cancer stem cells9:143; author reply 67, Nat Rev Cancer. Nuclear signalling by tumourassociated antigen EpCAM. Nat Cell Biol, vol.11, pp.162-71, 2009.

R. Linke, A. Klein, S. D. Catumaxomab, P. Wimberger, C. Kumper et al., Effective relief of malignant ascites in patients with advanced ovarian cancer by a trifunctional anti-EpCAM x anti-CD3 antibody: a phase I/II study Induction of anti-tumor immunity by trifunctional antibodies in patients with peritoneal carcinomatosis, MAbs. Clin Cancer Res. J Exp Clin Cancer Res. Immunobiology, vol.21328214, issue.70, pp.3899-90518, 2007.

K. Brischwein, B. Schlereth, B. Guller, C. Steiger, A. Wolf et al., MT110: A novel bispecific single-chain antibody construct with high efficacy in eradicating established tumors, Molecular Immunology, vol.43, issue.8, pp.1129-1172, 2006.
DOI : 10.1016/j.molimm.2005.07.034

A. Salnikov, A. Groth, A. Apel, G. Kallifatidis, B. Beckermann et al., Targeting of cancer stem cell marker EpCAM by bispecific antibody EpCAMxCD3 inhibits pancreatic carcinoma PAM4-reactive MUC1 is a biomarker for early pancreatic adenocarcinoma, J Cell Mol Med. Clin Cancer Res, vol.1313, pp.4023-337380, 2007.

D. Gold, R. Alisauskas, R. Sharkey, D. Gold, D. Goldenberg et al., Targeting of xenografted pancreatic cancer with a new monoclonal antibody, PAM4 A novel bispecific, trivalent antibody construct for targeting pancreatic carcinoma, Cancer Res. Cancer Res, vol.5568, issue.76, pp.1105-104819, 1995.

K. Ichikawa, W. Liu, L. Zhao, Z. Wang, D. Liu et al., Treatment with gemcitabine and TRA-8 anti-death receptor-5 mAb reduces pancreatic adenocarcinoma cell viability in vitro and growth in vivo1291-300; discussion 300. 79 Combination treatment with TRA-8 anti death receptor 5 antibody and CPT-11 induces tumor regression in an orthotopic model of pancreatic cancer TRA-8 anti-DR5 monoclonal antibody and gemcitabine induce apoptosis and inhibit radiologically validated orthotopic pancreatic tumor growth Phase I Trial of Weekly Tigatuzumab, an Agonistic Humanized Monoclonal Antibody Targeting Death Receptor 5 (DR5) al. Conatumumab, a fully human agonist antibody to death receptor 5, induces apoptosis via caspase activation in multiple tumor types Claudin 4 protein expression in primary and metastatic pancreatic cancer: support for use as a therapeutic target, DR5 monoclonal antibody without hepatocyte cytotoxicity, pp.954-605535, 2001.

M. Suzuki, M. Kato-nakano, S. Kawamoto, A. Furuya, Y. Abe et al., Therapeutic antitumor efficacy of monoclonal antibody against Claudin-4 for pancreatic and ovarian cancers, Cancer Science, vol.316, issue.9, pp.1623-1653, 2009.
DOI : 10.1111/j.1349-7006.2009.01239.x

M. Aubert, C. Franceschi, E. Mas, F. Silvy, and C. Crotte, the feto-acinar pancreatic protein targets pancreatic neoplastic tissues Monoclonal antibody 16D10 to the C-terminal domain of the feto-acinar pancreatic protein binds to membrane of human pancreatic tumoral SOJ-6 cells and inhibits the growth of tumor xenografts, Monoclonal antibody 16D10 to the COOH-terminal domain of, pp.282-91713, 2004.