New treatment options for advanced pancreatic cancer

References

• Parkin DM, Bray FI, Devesa SS. Cancer burden in the year 2000. The global picture. Eur. J. Cancer37 (Suppl. 8), 4–66 (2001).
   PubMed Web of Science ®Google Scholar
• Jemal A, Siegel R, Ward E et al. Cancer statistics 2008. CA Cancer J. Clin.58(2), 71–96 (2008).
   PubMed Web of Science ®Google Scholar
• Sultana A, Tudur Smith C, Cunningham D, Starling N, Neoptolemos JP, Ghaneh P. Meta-analyses of chemotherapy for locally advanced and metastatic pancreatic cancer. J. Clin. Oncol.25(18), 2607–2615 (2007).
   PubMed Web of Science ®Google Scholar
• Neoptolemos JP, Stocken DD, Friess H et al.; European Study Group for Pancreatic Cancer (ESPAC). A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N. Engl. J. Med.350(12), 1200–1210 (2004).
   PubMed Web of Science ®Google Scholar
• Oettle H, Post S, Neuhaus P et al. Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer, a randomized controlled trial. JAMA297(3), 267–277 (2007).
   PubMed Web of Science ®Google Scholar
• Yip D, Karapetis C, Strickland A, Steer CB, Goldstein D. Chemotherapy and radiotherapy for inoperable advanced pancreatic cancer. Cochrane Database Syst. Rev. Issue 3. DOI: 10.1002/14651858.CD002093.pub2. (2006).
   PubMedGoogle Scholar
• Sultana A, Tudur Smith C, Cunningham D et al. Systematic review, including meta-analyses, on the management of locally advanced pancreatic cancer using radiation/combined modality therapy. Br. J. Cancer96(8), 1183–1190 (2007).
   PubMed Web of Science ®Google Scholar
• Neoptolemos JP, Dunn JA, Stocken DD et al. Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: a randomised controlled trial. Lancet358(9293), 1576–1585 (2001).
   PubMed Web of Science ®Google Scholar
• Stocken DD, Buchler MW, Dervenis C et al. Meta-analysis of randomised adjuvant therapy trials for pancreatic cancer. Br. J. Cancer92(8), 1372–1381 (2005).
   PubMed Web of Science ®Google Scholar
• Smeenk HG, van Eijck CH, Hop WC et al. Long-term survival and metastatic pattern of pancreatic and periampullary cancer after adjuvant chemoradiation or observation: long-term results of EORTC trial 40891. Ann. Surg.246(5), 734–740 (2007).
   PubMed Web of Science ®Google Scholar
• Ghaneh P, Costello E, Neoptolemos JP. Biology and management of pancreatic cancer. Gut56, 1134–1152 (2007).
   PubMed Web of Science ®Google Scholar
• Pinkas-Kramarski R, Soussan L, Waterman H et al. Diversification of Neu differentiation factor and epidermal growth factor signaling by combinatorial receptor interactions. EMBO J.15(10), 2452–2467 (1996).
   PubMed Web of Science ®Google Scholar
• Friess H, Yamanaka Y, Kobrin MS, Do DA, Büchler MW, Korc M. Enhanced erbB-3 expression in human pancreatic cancer correlates with tumor progression. Clin. Cancer Res.1(11), 1413–1420 (1995).
   PubMed Web of Science ®Google Scholar
• Moore MJ, Goldstein D, Hamm J et al.; National Cancer Institute of Canada Clinical Trials Group. 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.25, 1960–1966 (2007).
   PubMed Web of Science ®Google Scholar
• Cunningham D, Humblet Y, Siena S et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N. Engl. J. Med.351(4), 337–345 (2004).
   PubMed Web of Science ®Google Scholar
• Gibson TB, Ranganathan A, Grothey A. Randomized Phase III trial results of panitumumab, a fully human anti-epidermal growth factor receptor monoclonal antibody, in metastatic colorectal cancer. Clin. Colorectal Cancer6(1), 29–31 (2006).
   PubMed Web of Science ®Google Scholar
• Ng SS, Tsao MS, Nicklee T, Hedley DW. Effects of the epidermal growth factor receptor inhibitor OSI-774, Tarceva, on downstream signaling pathways and apoptosis in human pancreatic adenocarcinoma. Mol. Cancer Ther.1(10), 777–783 (2002).
   PubMed Web of Science ®Google Scholar
• Sclabas GM, Fujioka S, Schmidt C, Fan Z, Evans DB, Chiao PJ. Restoring apoptosis in pancreatic cancer cells by targeting the nuclear factor-κB signaling pathway with the anti-epidermal growth factor antibody IMC-C225. J. Gastrointest. Surg.7(1), 37–43 (2003).
   PubMed Web of Science ®Google Scholar
• Xiong HQ, Rosenberg A, LoBuglio A 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. J. Clin. Oncol.22(13), 2610–2616 (2004).
   PubMed Web of Science ®Google Scholar
• Philip PA, Benedetti J, Fenoglio-Preiser C et al. Phase III study of gemcitabine plus cetuximab versus gemcitabine in patients with locally advanced or metastatic pancreatic adenocarcinoma: SWOG S0205 study. J. Clin. Oncol. 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Suppl.), LBA4509 (2007).
   Google Scholar
• Safran H, Iannitti D, Miner TK et al. GW572016, gemcitabine and GW572016, gemcitabine, oxaliplatin, a two-stage, Phase I study for advanced pancreaticobiliary cancer. J. Clin. Oncol. 2006 ASCO Annual Meeting Proceedings Part I. Vol 24, No. 18S (June 20 Suppl.), 4002 (2006).
   Google Scholar
• Safran H, Iannitti D, Miner TP et al. GW572016/gemcitabine and GW572016/gemcitabine/oxaliplatin, a two-stage, Phase I study for advanced pancreaticobiliary cancer. J. Clin. Oncol. 2006 Gastrointestinal Cancers Symposium: 124.
   Google Scholar
• Spector NL, Yarden Y, Smith B et al. Activation of AMP-activated protein kinase by human EGF receptor 2/EGF receptor tyrosine kinase inhibitor protects cardiac cells. Proc. Natl Acad. Sci. USA104(25), 10607–10612 (2007).
   PubMed Web of Science ®Google Scholar
• Blaszkowsky LS, Ryan DP, Earle C et al. A Phase II study of docetaxel in combination with ZD1839 (gefitinib) in previously treated patients with metastatic pancreatic cancer. J. Clin. Oncol. 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Suppl.), 15080 (2007).
   Google Scholar
• Fountzilas G, Murray S, Xiros N et al. Gemcitabine combined with gefitinib in patients with inoperable or metastatic pancreatic cancer. A Phase II trial. J. Clin. Oncol. 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Suppl.), 15016 (2007).
   Google Scholar
• Berger DH, Jardines LA, Chang H, Ruggeri B. Activation of Raf-1 in human pancreatic adenocarcinoma. J. Surg. Res.69(1), 199–204 (1997).
   PubMedGoogle Scholar
• Yip-Schneider MT, Lin A, Barnard D, Sweeney CJ, Marshall MS. Lack of elevated MAP kinase (Erk) activity in pancreatic carcinomas despite oncogenic K-ras expression. Int. J. Oncol.15(2), 271–279 (1999).
   PubMed Web of Science ®Google Scholar
• Yip-Schneider MT, Lin A, Marshall MS. Pancreatic tumor cells with mutant K-ras suppress ERK activity by MEK-dependent induction of MAP kinase phosphatase-2. Biochem. Biophys. Res. Commun.280(4), 992–997 (2001).
   PubMed Web of Science ®Google Scholar
• Yip-Schneider MT, Schmidt CM. MEK inhibition of pancreatic carcinoma cells by U0126 and its effect in combination with sulindac. Pancreas27(4), 337–344 (2003).
   PubMedGoogle Scholar
• Davies BR, Logie A, McKay JS et al. AZD6244 (ARRY-142886), a potent inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1/2 kinases, mechanism of action in vivo, pharmacokinetic/pharmacodynamic relationship, and potential for combination in preclinical models. Mol. Cancer Ther.6(8), 2209–2219 (2007).
   PubMed Web of Science ®Google Scholar
• Yeh TC, Marsh V, Bernat BA et al. Biological characterization of ARRY-142886 (AZD6244), a potent, highly selective mitogen-activated protein kinase kinase 1/2 inhibitor. Clin. Cancer Res.13(5), 1576–1583 (2007).
   PubMed Web of Science ®Google Scholar
• Haklai R, Elad-Sfadia G, Egozi Y, Kloog Y. Orally administered FTS (salirasib) inhibits human pancreatic tumor growth in nude mice. Cancer Chemother. Pharmacol.61(1), 89–96 (2008).
   PubMed Web of Science ®Google Scholar
• Rudek MA, Khan Y, Goldsweig H et al. Integrated development of S-Trans, Trans-Farnesylthiosalicylic acid (FTS, Salisarib) in pancreatic cancer. J. Clin. Oncol. 2008 ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol 26, No 15S (May 20 Suppl.), 4626 (2008).
   PubMedGoogle Scholar
• Tice DA, Biscardi JS, Nickles AL, Parsons SJ. Mechanism of biological synergy between cellular Src and epidermal growth factor receptor. Proc. Natl Acad. Sci. USA96(4), 1415–1420 (1999).
   PubMed Web of Science ®Google Scholar
• Biscardi JS, Maa MC, Tice DA, Cox ME, Leu TH, Parsons SJ. c-Src-mediated phosphorylation of the epidermal growth factor receptor on Tyr845 and Tyr1101 is associated with modulation of receptor function. J. Biol. Chem.274(12), 8335–8343 (1999).
   PubMed Web of Science ®Google Scholar
• Kloth MT, Laughlin KK, Biscardi JS, Boerner JL, Parsons SJ, Silva CM. STAT5b, a mediator of synergism between c-Src and the epidermal growth factor receptor. J. Biol. Chem.278(3), 1671–1679 (2003).
   PubMedGoogle Scholar
• Brunton VG, Avizienyte E, Fincham VJ et al. Identification of Src-specific phosphorylation site on focal adhesion kinase, dissection of the role of Src SH2 and catalytic functions and their consequences for tumor cell behavior. Cancer Res.65(4), 1335–1342 (2005).
   PubMed Web of Science ®Google Scholar
• Summy JM, Trevino JG, Baker CH, Gallick GE. c-Src regulates constitutive and EGF-mediated VEGF expression in pancreatic tumor cells through activation of phosphatidyl inositol-3 kinase and p38 MAPK. Pancreas31(3), 263–274 (2005).
   PubMedGoogle Scholar
• Trevino JG, Summy JM, Gray MJ et al. Expression and activity of SRC regulate interleukin-8 expression in pancreatic adenocarcinoma cells, implications for angiogenesis. Cancer Res.65(16), 7214–7222 (2005).
   PubMed Web of Science ®Google Scholar
• Lutz MP, Esser IB, Flossmann-Kast BB et al. Overexpression and activation of the tyrosine kinase Src in human pancreatic carcinoma. Biochem. Biophys. Res. Commun.243(2), 503–508 (1998).
   PubMed Web of Science ®Google Scholar
• Duxbury MS, Ito H, Zinner MJ, Ashley SW, Whang EE. Inhibition of SRC tyrosine kinase impairs inherent and acquired gemcitabine resistance in human pancreatic adenocarcinoma cells. Clin. Cancer Res.10(7), 2307–2318 (2004).
   PubMed Web of Science ®Google Scholar
• Yezhelyev MV, Koehl G, Guba M. Inhibition of SRC tyrosine kinase as treatment for human pancreatic cancer growing orthotopically in nude mice. Clin. Cancer Res.10(23), 8028–8036 (2004).
   PubMed Web of Science ®Google Scholar
• Hennequin LF, Allen J, Breed J et al.N-(5-chloro-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5-(tetrahydro-2H-pyran-4-yloxy)quinazolin-4-amine, a novel, highly selective, orally available, dual-specific c-Src/Abl kinase inhibitor. J. Med. Chem.49(22), 6465–6488 (2006).
   PubMed Web of Science ®Google Scholar
• Trevino JG, Summy JM, Lesslie DP et al. Inhibition of SRC expression and activity inhibits tumor progression and metastasis of human pancreatic adenocarcinoma cells in an orthotopic nude mouse model. Am. J. Pathol.168(3), 962–972 (2006).
   PubMed Web of Science ®Google Scholar
• Messersmith WA, Krishnamurthi S, Hewes BA et al. Bosutinib (SKI-606), a dual Src/Abl tyrosine kinase inhibitor, preliminary results from a Phase 1 study in patients with advanced malignant solid tumors. J. Clin. Oncol. 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Suppl.), 3552 (2007).
   PubMedGoogle Scholar
• Shaw RJ, Cantley LC. Ras, PI(3)K and mTOR signalling controls tumour cell growth. Nature441(7092), 424–430 (2006).
   PubMed Web of Science ®Google Scholar
• Karin M. Nuclear factor-κ B in cancer development and progression. Nature441(7092), 431–436 (2006).
   PubMed Web of Science ®Google Scholar
• Chen F, Castranova V. Nuclear factor-κ B, an unappreciated tumor suppressor. Cancer Res.67(23), 11093–11098 (2007).
   PubMed Web of Science ®Google Scholar
• Khanbolooki S, Nawrocki ST, Arumugam T et al. Nuclear factor-κB maintains TRAIL resistance in human pancreatic cancer cells. Mol. Cancer Ther.5(9), 2251–2260 (2006).
   PubMed Web of Science ®Google Scholar
• Verma A, Guha S, Wang H et al. Tissue transglutaminase regulates focal adhesion kinase/AKT activation by modulating PTEN expression in pancreatic cancer cells. Clin. Cancer Res.14(7), 1997–2005 (2008).
   PubMed Web of Science ®Google Scholar
• Liu W, Bloom DA, Cance WG et al. FAK and IGF-IR interact to provide survival signals in human pancreatic adenocarcinoma cells. Carcinogenesis29(6), 1096–1107 (2008).
   PubMed Web of Science ®Google Scholar
• Garcia JA, Danielpour D. Mammalian target of rapamycin inhibition as a therapeutic strategy in the management of urologic malignancies. Mol. Cancer Ther.7(6), 1347–1354 (2008).
   PubMed Web of Science ®Google Scholar
• Wolpin BM, Hezel AF, Ryan DP et al. Phase II study of RAD001 in previously treated patients with metastatic pancreatic cancer. J. Clin. Oncol. 2008 ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol 26, No 15S (May 20 Suppl.), 4614 (2008).
   Google Scholar
• Ito D, Fujimoto K, Mori Tet al.In vivo antitumor effect of the mTOR inhibitor CCI-779 and gemcitabine in xenograft models of human pancreatic cancer. Int. J. Cancer118, 2337–2343 (2006).
   PubMed Web of Science ®Google Scholar
• Ryan DP, O’Neil BH, Supko JG et al. A Phase I study of bortezomib plus irinotecan in patients with advanced solid tumors. Cancer107, 2688–2697 (2006).
   PubMed Web of Science ®Google Scholar
• Dhillon N, Aggarwal BB, Newman RA et al. Phase II trial of curcumin in patients with advanced pancreatic cancer. Clin. Cancer Res.14(14), 4491–4499 (2008).
   PubMed Web of Science ®Google Scholar
• Epelbaum R, Vizel B, Bar-Sela G. Phase II study of curcumin and gemcitabine in patients with advanced pancreatic cancer. J. Clin. Oncol. 2008 ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol 26, No 15S (May 20 Suppl.), 15619 (2008).
   Google Scholar
• Ellis LM, Hicklin DJ. VEGF-targeted therapy, mechanisms of anti-tumour activity. Nat. Rev. Cancer8(8), 579–591 (2008).
   PubMed Web of Science ®Google Scholar
• Ciardiello F, Caputo R, Damiano V et al. Antitumor effects of ZD6474, a small molecule vascular endothelial growth factor receptor tyrosine kinase inhibitor, with additional activity against epidermal growth factor receptor tyrosine kinase. Clin. Cancer Res.9(4), 1546–1556 (2003).
   PubMed Web of Science ®Google Scholar
• Kindler HL, Niedzwiecki D, Hollis D et al. 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) 80303. J. Clin. Oncol. Gastrointestinal Cancers Symposium, 108 (2007).
   Google Scholar
• Vervenne W, Bennouna J, Humblet Y et al.A randomized, double-blind, placebo (P) controlled, multicenter Phase III trial to evaluate the efficacy and safety of adding bevacizumab (B) to erlotinib (E) and gemcitabine (G) in patients (pts) with metastatic pancreatic cancer. J. Clin. Oncol. 2008 ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol 26, No 15S (May 20 Suppl.), 4507 (2008).
   PubMedGoogle Scholar
• Kindler HL, Gangadhar T, Karrison T et al.Final analysis of a randomized Phase II study of bevacizumab (B) and gemcitabine (G) plus cetuximab (C) or erlotinib (E) in patients (pts) with advanced pancreatic cancer (PC).J. Clin. Oncol. 2008 ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol 26, No 15S (May 20 Suppl.), 4502 (2008).
   Google Scholar
• Kindler HL, Friberg G, Singh DA et al. Phase II trial of bevacizumab plus gemcitabine in patients with advanced pancreatic cancer. J. Clin. Oncol.23(31), 8033–8040 (2005).
   PubMed Web of Science ®Google Scholar
• Ko AH, Dito E, Schillinger B et al. A Phase II study of bevacizumab (BEV) plus erlotinib (ERL) in patients with gemcitabine (GEM)-refractory metastatic pancreatic cancer (MPC).J. Clin. Oncol. 2008 ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol 26, No 15S (May 20 Suppl.), 4516 (2008).
   PubMedGoogle Scholar
• Spano J, Chodkiewicz C, Maurel J et al. Efficacy of gemcitabine plus axitinib compared with gemcitabine alone in patients with advanced pancreatic cancer, an open-label randomised Phase II study. Lancet371(9630), 2101–2108 (2008).
   PubMed Web of Science ®Google Scholar
• Conrad C, Ischenko I, Köhl G et al. Antiangiogenic and antitumor activity of a novel vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor ZD6474 in a metastatic human pancreatic tumor model. Anticancer Drugs18(5), 569–579 (2007).
   PubMedGoogle Scholar
• Wedge SR, Kendrew J, Hennequin LF et al. AZD2171, a highly potent, orally bioavailable, vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for the treatment of cancer. Cancer Res.65(10), 4389–4400 (2005).
   PubMed Web of Science ®Google Scholar
• Thomas AL, Morgan B, Horsfield MA et al. Phase I study of the safety, tolerability, pharmacokinetics, and pharmacodynamics of PTK787/ZK 222584 administered twice daily in patients with advanced cancer. J. Clin. Oncol.23(18), 4162–4171 (2005).
   PubMed Web of Science ®Google Scholar
• Kuo T, Cabebe EC, Koong A et al. An update of a Phase I/II study of the VEGF receptor tyrosine kinase inhibitor vatalanib and gemcitabine in patients with advanced pancreatic cance. J. Clin. Oncol. 2008 ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol 26, No 15S (May 20 Suppl.), 15571. 60 (2008).
   PubMedGoogle Scholar
• Dragovich T, Laheru DA, Crowley JJ et al.Phase II trial of vatalinib in patients with advanced or metastatic pancreatic adenocarcinoma who failed gemcitabine therapy. J. Clin. Oncol. 2008 ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol 26, No 15S (May 20 Suppl.), 4615 (2008).
   Google Scholar
• Cao, R. Björndahl MA, Religa P et al. PDGF-BB induces intratumoral lymphangiogenesis and promotes lymphatic metastasis. Cancer Cell6, 333–345 (2004).
   PubMed Web of Science ®Google Scholar
• Bergers G, Song S, Meyer-Morse N, Bergsland E, Hanahan D. Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors. J. Clin. Invest.111(9), 1287–1295 (2003).
   PubMed Web of Science ®Google Scholar
• Jain RK, Lahdenranta J, Fukumura D. Targeting PDGF signaling in carcinoma-associated fibroblasts controls cervical cancer in mouse model. PLoS Med.5(1), E24 (2008).
   Google Scholar
• Whartenby KA, Calabresi PA, McCadden. Inhibition of FLT3 signaling targets DCs to ameliorate autoimmune disease. Proc. Natl Acad. Sci. U.S.A.102(46), 16741–16746 (2005).
   PubMed Web of Science ®Google Scholar
• Ryschich E, Huszty G, Wentzensen N et al. Effect of Flt3 ligand gene transfer in experimental pancreatic cancer. Int. J. Colorectal. Dis.22(2), 215–223 (2007).
   PubMedGoogle Scholar
• Li J, Kleeff J, Guo J et al. Effects of STI571 (gleevec) on pancreatic cancer cell growth. Mol. Cancer2, 32 (2003).
   PubMedGoogle Scholar
• Hwang RF, Yokoi K, Bucana CD et al. Inhibition of platelet-derived growth factor receptor phosphorylation by STI571 (Gleevec) reduces growth and metastasis of human pancreatic carcinoma in an orthotopic nude mouse model. Clin. Cancer Res.9(17), 6534–6544 (2003).
   PubMed Web of Science ®Google Scholar
• Chen J, Rocken C, Nitsche B et al. The tyrosine kinase inhibitor imatinib fails to inhibit pancreatic cancer progression. Cancer Lett.233(2), 328–337 (2006).
   PubMed Web of Science ®Google Scholar
• Lyons JF, Wilhelm S, Hibner B, Bollag G. Discovery of a novel Raf kinase inhibitor. Endocr. Relat. Cancer.8(3), 219–225 (2001).
   PubMed Web of Science ®Google Scholar
• Vincent P, Zhang X, Chen C et al. Chemotherapy with the raf kinase inhibitor BAY 43–9006 in combination with irinotecan, vinorelbine, or gemcitabine is well tolerated and efficacious in preclinical xenograft models. Proc. Am. Soc. Clin. Oncol.21, (2002) (Abstract 1900).
   Google Scholar
• Siu LL, Awada A, Takimoto CH et al. Phase I trial of sorafenib and gemcitabine in advanced solid tumors with an expanded cohort in advanced pancreatic cancer. Clin. Cancer Res.12(1), 144–151 (2006).
   PubMed Web of Science ®Google Scholar
• Wallace JA, Locker G, Nattam S et al.Sorafenib (S) plus gemcitabine (G) for advanced pancreatic cancer (PC). A Phase II trial of the University of Chicago Phase II Consortium. J. Clin. Oncol. 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Suppl.), 4608 (2007).
   Google Scholar
• de Jonge MJ, Verweij J. Multiple targeted tyrosine kinase inhibition in the clinic, all for one or one for all? Eur. J. Cancer42, 1351–1356 (2006).
   PubMedGoogle Scholar
• O’Reilly EM, Niedzwiecki D, Hollis DR et al. A Phase II trial of sunitinib (S) in previously-treated pancreas adenocarcinoma (PAC), CALGB 80603. J. Clin. Oncol. 2008 ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol 26, No. 15S (May 20 Suppl.), 4515 (2008) .
   Google Scholar
• Chu TF, Rupnick MA, Kerkela R et al. Cardiotoxicity associated with tyrosine kinase inhibitor sunitinib. Lancet370(9604), 2011–2019 (2007).
   PubMed Web of Science ®Google Scholar
• Bentle MS, Reinicke KE, Dong Y, Bey EA, Boothman DA. Nonhomologous end joining is essential for cellular resistance to the novel antitumor agent, β-lapachone. Cancer Res.67(14), 6936–6945 (2007).
   PubMed Web of Science ®Google Scholar
• Khong HT, Dreisbach L, Kindler HL et al. A Phase 2 study of ARQ 501 in combination with gemcitabine in adult patients with treatment naive, unresectable pancreatic adenocarcinoma. J. Clin. Oncol. 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Suppl.), 15017 (2007).
   Google Scholar
• Deeb KK, Trump DL, Johnson CS. Vitamin D signalling pathways in cancer, potential for anticancer therapeutics. Nat. Rev. Cancer7(9), 684–700 (2007).
   PubMed Web of Science ®Google Scholar
• Lopez CD, Beer T, Todd K, Blanke CD. A Phase II trial of high-dose calcitriol and docetaxel in patients with untreated, incurable pancreatic adenocarcinoma. J. Clin. Oncol. 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Suppl.), 15099 (2007).
   Google Scholar
• Wiedmann M, Haefner M, Niederhagen M et al. Treatment of pancreatic cancer with two novel histone deacetylase inhibitors NVP-LAQ824 and NVP-LBH589. J. Clin. Oncol. 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Suppl.), 4624 (2007).
   Google Scholar
• Aguilar-Quesada R, Muñoz-Gámez JA et al. Modulation of transcription by PARP-1, consequences in carcinogenesis and inflammation. Curr. Med. Chem.14(11), 1179–1187 (2007).
   PubMed Web of Science ®Google Scholar
• Burkitt M, Magee C, O’Connor D, Campbell F, Cornford P, Greenhalf W. Potentiation of chemotherapeutics by the Hsp90 antagonist geldanamycin requires a steady serum condition. Mol. Carcinog.46(6), 466–475 (2007).
   PubMed Web of Science ®Google Scholar
• Lang SA, Moser C, Gaumann A et al. Targeting heat shock protein 90 in pancreatic cancer impairs insulin-like growth factor-i receptor signaling, disrupts an interleukin-6/signal-transducer and activator of transcription 3/hypoxia-inducible factor-1α autocrine loop, and reduces orthotopic tumor growth. Clin. Cancer Res.13, 6459–6468 (2007).
   PubMed Web of Science ®Google Scholar
• Feldmann G, Dhara S, Fendrich V et al. Blockade of Hedgehog signaling inhibits pancreatic cancer invasion and metastases, a new paradigm for combination therapy in solid cancers. Cancer Res.67(5), 2187–2196 (2007).
   PubMed Web of Science ®Google Scholar
• Gilboa E. The promise of cancer vaccines. Nat. Rev. Cancer4(5), 401–411 (2004).
   PubMed Web of Science ®Google Scholar
• Lake RA, Robinson BW. Immunotherapy and chemotherapy – a practical partnership. Nat. Rev. Cancer5(5), 397–405 (2005).
   PubMed Web of Science ®Google Scholar
• Williams MA, Tyznik AJ, Bevan MJ. Interleukin-2 signals during priming are required for secondary expansion of CD8+ memory T cells. Nature441(7095), 890–893 (2006).
   PubMed Web of Science ®Google Scholar
• Ryschich E, Notzel T, Hinz U et al. Control of T-cell-mediated immune response by HLA class I in human pancreatic carcinoma. Clin. Cancer Res.11(2 Pt 1), 498–504 (2005).
   PubMed Web of Science ®Google Scholar
• Levitsky HI, Lazenby A, Hayashi RJ, Pardoll DM. In vivo priming of two distinct antitumor effector populations, the role of MHC class I expression. J. Exp. Med.179(4), 1215–1224 (1994).
   PubMed Web of Science ®Google Scholar
• Shi Y, Zheng W, Rock KL. Cell injury releases endogenous adjuvants that stimulate cytotoxic T cell responses. Proc. Natl Acad. Sci. USA97(26), 14590–14595 (2000).
   PubMed Web of Science ®Google Scholar
• Shi Y, Evans JE, Rock KL. Molecular identification of a danger signal that alerts the immune system to dying cells. Nature425(6957), 516–521 (2003).
   PubMed Web of Science ®Google Scholar
• Demaria S, Santori FR, Ng B, Liebes L, Formenti SC, Vukmanovic S. Select forms of tumor cell apoptosis induce dendritic cell maturation. J. Leukoc. Biol.77(3), 361–368 (2005).
   PubMed Web of Science ®Google Scholar
• Petak I, Tillman DM, Houghton JA. p53 dependence of Fas induction and acute apoptosis in response to 5-fluorouracil-leucovorin in human colon carcinoma cell lines. Clin. Cancer Res.6(11), 4432–4441 (2000).
   PubMedGoogle Scholar
• Nowak AK, Robinson BW, Lake RA. Synergy between chemotherapy and immunotherapy in the treatment of established murine solid tumors. Cancer Res.63(15), 4490–4496 (2003).
   PubMed Web of Science ®Google Scholar
• Nowak AK, Lake RA, Marzo AL et al. Induction of tumor cell apoptosis in vivo increases tumor antigen cross-presentation, cross-priming rather than cross-tolerizing host tumor-specific CD8 T cells. J. Immunol.170(10), 4905–4913 (2003).
   PubMed Web of Science ®Google Scholar
• Bernhardt SL, Gjertsen MK, Trachsel S et al. Telomerase peptide vaccination of patients with non-resectable pancreatic cancer, a dose escalating Phase I/II study. Br. J. Cancer95(11), 1474–1482 (2006).
   PubMed Web of Science ®Google Scholar
• Cunningham D, Chau I, Stocken D et al. Phase III randomised comparison of gemcitabine versus gemcitabine plus capecitabine in patients with advanced pancreatic cancer. Eur. J. Cancer3(4 Suppl. 12), (2005) (Abstract PS11).
   Google Scholar
• Herrmann R, Bodoky G, Ruhstaller T et al, Swiss Group for Clinical Cancer Research; Central European Cooperative Oncology Group. Gemcitabine plus capecitabine compared with gemcitabine alone in advanced pancreatic cancer, a randomized, multicenter, Phase III trial of the Swiss Group for Clinical Cancer Research and the Central European Cooperative Oncology Group. J. Clin. Oncol.25(16), 2212–2217 (2007).
   PubMed Web of Science ®Google Scholar
• Sultana A, Tudur Smith C, Cunningham D et al. Gemcitabine-based combination chemotherapy in advanced pancreatic cancer-indirect comparison. BMC Cancer8, 192 (2008).
   PubMedGoogle Scholar
• Sultana A, Tudur Smith C, Cunningham D et al. Meta-analyses of chemotherapy for locally advanced and metastatic pancreatic cancer, results of secondary end points analyses. Br. J. Cancer99(1), 6–13 (2008).
   PubMed Web of Science ®Google Scholar
• Mitry E, Dahan L, Ychou M et al. LV5FU2-cisplatin followed by gemcitabine or the reverse sequence in metastatic pancreatic cancer, preliminary results of a randomized Phase III trial (FFCD 0301). J. Clin. Oncol. 2008 ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol 26, No 15S (May 20 Suppl.), 4513 (2008).
   Google Scholar
• Starling N, Neoptolemos J, Cunningham D. Role of erlotinib in the management of pancreatic cancer. Ther. Clin. Risk Manag.2(4), 435–445 (2006).
   PubMedGoogle Scholar
• Pelzer U, Kubica K, Stieler J et al. A randomized trial in patients with gemcitabine refractory pancreatic cancer. Final results of the CONKO 003 study. J. Clin. Oncol. 2008 ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol 26, No 15S (May 20 Suppl.), 4508 (2008).
   Google Scholar
• Smith DB, Neoptolemos JP. Capecitabine in carcinoma of the pancreas. Expert Opin. Pharmacother.7(12), 1633–1639 (2006).
   PubMed Web of Science ®Google Scholar
• Oh D, Lee K, Lee K et al. A Phase II trial of erlotinib in combination with gemcitabine and capecitabine in previously untreated metastatic/recurrent pancreatic cancer. J. Clin. Oncol. 2008 ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol 26, No 15S (May 20 Suppl.), 4638 (2008).
   Google Scholar
• Okusaka T, Funakoshi A, Furuse J et al. A late Phase II study of S-1 for metastatic pancreatic cancer. Cancer Chemother. Pharmacol.61(4), 615–621 (2008).
   PubMed Web of Science ®Google Scholar
• Lee G, Kim H, Kang M et al. Phase II trial of S-1 in combination with gemcitabine in chemo-naive patients with locally advanced or metastatic pancreatic cancer. J. Clin. Oncol. 2008 ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol 26, No. 15S (May 20 Suppl.), 15577 (2008).
   Google Scholar
• Nakamura K, Yamaguchi T, Ishihara T et al. Phase II trial of oral S-1 combined with gemcitabine in metastatic pancreatic cancer. Br. J. Cancer94(11), 1575–1579 (2006).
   PubMed Web of Science ®Google Scholar
• Chauffert B, Mornex F, Bonnetain F et al. 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 2000–2001 FFCD/SFRO study. Ann. Oncol.19(9), 1592–1599 (2008).
   PubMed Web of Science ®Google Scholar
• Loehrer PJ, Powell ME, Cardenes HR et al. A randomized Phase III study of gemcitabine in combination with radiation therapy versus gemcitabine alone in patients with localized, unresectable pancreatic cancer. J. Clin. Oncol. 2008 ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol 26, No. 15S (May 20 Suppl.), E420 (2008).
   Google Scholar
• Neuhaus P, Riess H, Post S et al. CONKO-001, Final results of the randomized, prospective, multicenter Phase III trial of adjuvant chemotherapy with gemcitabine versus observation in patients with resected pancreatic cancer (PC). J. Clin. Oncol. 2008 ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol 26, No. 15S (May 20 Suppl.), LBA4504 (2008).
   Google Scholar
• Posner M, Chang KJ, Rosemurgy A et al. Multi-center Phase II/III randomized controlled clinical trial using TNFerade combined with chemoradiation in patients with locally advanced pancreatic cancer (LAPC). J. Clin. Oncol. 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Suppl.), 4518 (2007).
   Google Scholar
• Aung KL, Smith DB, Neoptolemos JP. Adjuvant therapy for pancreatic cancer. Expert Opin. Pharmacother.8(15), 2533–2541 (2007).
   PubMed Web of Science ®Google Scholar
• Maeda A, Boku N, Fukutomi A et al.; Japan Adjuvant Study Group of Pancreatic Cancer (JASPAC-01). Randomized Phase III trial of adjuvant chemotherapy with gemcitabine versus S-1 in patients with resected pancreatic cancer. Jpn. J. Clin. Oncol.38(3), 227–229 (2008).
   PubMed Web of Science ®Google Scholar
• Neoptolemos JP. Clinical evidence does not support the use of adjuvant radiotherapy in pancreatic cancer. Nat. Clin. Pract. Oncol.5(8), 431 (2008).
   PubMedGoogle Scholar
• Regine WF, Winter KW, Abrams R et al. Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma, a randomized controlled trial. JAMA299(9), 1019–1026 (2008).
   PubMed Web of Science ®Google Scholar
• Picozzi VJ, Abrams RA, Traverso LW et al. ACOSOG Z05031, report on a multicenter, Phase II trial for adjuvant therapy of resected pancreatic cancer using cisplatin, 5-FU, and α-interferon. J. Clin. Oncol. 2008 ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol 26, No 15S (May 20 Suppl.), 4505 (2008).
   Google Scholar
• Van Laethem JE, Van Cutsem E, Hammel P et al.Adjuvant chemotherapy alone versus chemoradiation after curative resection for pancreatic cancer, feasibility results of a randomised EORTC/FFCD/GERCOR Phase II/III study (40013/22012/0304). J. Clin. Oncol. 2008 ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol 26, No. 15S (May 20 Suppl.), 4514 (2008).
   PubMedGoogle Scholar
• Biswas S, Guix M, Rinehart C et al. Inhibition of TGF-β with neutralizing antibodies prevents radiation-induced acceleration of metastatic cancer progression. J. Clin. Invest.117(5), 1305–1313 (2007).
   PubMed Web of Science ®Google Scholar
• Real FX. A ‘catastrophic hypothesis’ for pancreas cancer progression. Gastroenterology124(7), 1958–1964 (2003).
   PubMedGoogle Scholar