Brief overview of selected approaches in targeting pancreatic adenocarcinoma

Bibliography

• Siegel R, Naishadham D, Jemal A. Cancer statistics 2012. CA Cancer J Clin 2012;62(1):10-29
   PubMed Web of Science ®Google Scholar
• Muniraj T, Jamidar PA, Aslanian HR. Pancreatic cancer: a comprehensive review and update. Dis Mon 2013;59(11):368-402
   PubMed Web of Science ®Google Scholar
• Neuzillet C, Hammel P, Tijeras-Raballand A, et al. Targeting the Ras-ERK pathway in pancreatic adenocarcinoma. Cancer Metastasis Rev 2013;32(1-2):147-62
   PubMed Web of Science ®Google Scholar
• Belda-Iniesta C, Ibáñez de Cáceres I, Barriuso J, et al. Molecular biology of pancreatic cancer. Clin Transl Oncol 2008;10(9):530-7
   PubMed Web of Science ®Google Scholar
• Morris JP IV, Wang SC, Hebrok M. Review KRAS, Hedgehog, Wnt and the twisted developmental biology of pancreatic ductal adenocarcinoma. Nat Rev Cancer 2010;10(10):683-95
   PubMed Web of Science ®Google Scholar
• Collins MA, Bednar F, Zhang Y, et al. Oncogenic Kras is required for both the initiation and maintenance of pancreatic cancer in mice. J Clin Invest 2012;122(2):639-53
   PubMed Web of Science ®Google Scholar
• Avila JL, Kissil JL. Notch signaling in pancreatic cancer: oncogene or tumor suppressor? Trends Mol Med 2013;19(5):320-7
   PubMed Web of Science ®Google Scholar
• Fehrenbacher N, Bar-Sagi D, Philips M. Ras/MAPK signaling from endomembranes. Mol Oncol 2009;3(4):297-307
   PubMed Web of Science ®Google Scholar
• Jones S, Zhang X, Parsons DW, et al. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science 2008;321(5897):1801-6
   PubMed Web of Science ®Google Scholar
• Young SG, Yang SH, Davies BS, et al. Targeting protein prenylation in progeria. Sci Transl Med 2013;5(171):171ps3
   PubMed Web of Science ®Google Scholar
• Mackenzie GG, Bartels LE, Xie G, et al. A novel Ras inhibitor (MDC-1016) reduces human pancreatic tumor growth in mice. Neoplasia 2013;15(10):1184-95
   PubMed Web of Science ®Google Scholar
• Rotblat B, Ehrlich M, Haklai R, Kloog Y. The Ras inhibitor farnesylthiosalicylic acid (Salirasib) disrupts the spatiotemporal localization of active Ras: a potential treatment for cancer. Methods Enzymol 2008;439:467-89
   PubMed Web of Science ®Google Scholar
• Riely GJ, Johnson ML, Medina C, et al. A phase II trial of salirasib in patients with lung adenocarcinomas with KRAS mutations. J Thorac Oncol 2011;6(8):1435-7
   PubMed Web of Science ®Google Scholar
• Zorde Khvalevsky E, Gabai R, Rachmut IH, et al. Mutant KRAS is a druggable target for pancreatic cancer. Proc Natl Acad Sci USA 2013;110(51):20723-8
   PubMed Web of Science ®Google Scholar
• Golan T, Hubert A, Shemi A, et al. A phase I trial of a local delivery of siRNA against k-ras in combination with chemotherapy for locally advanced pancreatic adenocarcinoma. J Clin Oncol 2103;31(Suppl):abstract #4037
   Google Scholar
• Strimpakos AS, Saif MW. Update on phase I studies in advanced pancreatic adenocarcinoma. Hunting in darkness? JOP 2013;14(4):354-8
   PubMedGoogle Scholar
• Akinleye A, Furqan M, Mukhi N, et al. MEK and the inhibitors: from bench to bedside. J Hematol Oncol 2013;6:27
   PubMed Web of Science ®Google Scholar
• Polivka J Jr, Janku F. Molecular targets for cancer therapy in the PI3K/AKT/mTOR pathway. Pharmacol Ther 2013. [Epub ahead of print]
   PubMed Web of Science ®Google Scholar
• Zhong H, Sanchez C, Spitrzer D, et al. Synergistic effects of concurrent blockade of PI3K and MEK pathways in pancreatic cancer preclinical models. PLoS One 2013;8(10):e77243
   PubMed Web of Science ®Google Scholar
• Hofmann I, Weiss A, Elain G, et al. K-RAS mutant pancreatic tumors show higher sensitivity to MEK than to PI3K inhibition in vivo. PLoS One 2012;7(8):e44146
   PubMed Web of Science ®Google Scholar
• Troiani T, Martinelli E, Capasso A, et al. Targeting EGFR in pancreatic cancer treatment. Curr Drug Targets 2012;13(6):802-10
   PubMed Web of Science ®Google Scholar
• Tomas A, Futter CE, Eden ER. EGF receptor trafficking: consequences for signaling and cancer. Trends Cell Biol 2014;24(1):26-34
   PubMed Web of Science ®Google Scholar
• Maron R, Schechter B, Mancini M, et al. Inhibition of pancreatic carcinoma by homo- and heterocombinations of antibodies against EGF-receptor and its kin HER2/ErbB-2. Proc Natl Acad Sci USA 2013;110(38):15389-94
   PubMed Web of Science ®Google Scholar
• Mahipal A, Kothari N, Gupta S. Epidermal growth factor receptor inhibitors: coming of age. Cancer Control 2014;21(1):74-9
   PubMed Web of Science ®Google Scholar
• Faloppi L, Andrikou K, Cascinu S. Cetuximab: still an option in the treatment of pancreatic cancer? Expert Opin Biol Ther 2013;13(5):791-801
   PubMed Web of Science ®Google Scholar
• Ramanujan S, Pluen A, McKee TD, et al. Diffusion and convection in collagen gels: implications for transport in the tumor interstitium. Biophys J 2002;83(3):1650-60
   PubMed Web of Science ®Google Scholar
• Yonezawa S, Asai T, Oku N. Effective tumor regression by anti-neovascular therapy in hypovascular orthotopic pancreatic tumor model. J Control Release 2007;118(3):303-9
   PubMed Web of Science ®Google Scholar
• Provenzano PP, Hingorani SR. Hyaluronan, fluid pressure, and stromal resistance in pancreas cancer. Br J Cancer 2013;108(1):1-8
   PubMed Web of Science ®Google Scholar
• Hamada S, Masamune A, Shimosegawa T. Alteration of pancreatic cancer cell functions by tumor-stromal cell interaction. Front Physiol 2013;4:318
   Google Scholar
• Lunardi S, Muschel RJ, Brunner TB. The stromal compartments in pancreatic cancer: are there any therapeutic targets? Cancer Lett 2014;343(2):147-55
   PubMed Web of Science ®Google Scholar
• Neesse A, Krug S, Gress TM, et al. Emerging concepts in pancreatic cancer medicine: targeting the tumor stroma. Onco Targets Ther 2013;7:33-43
   PubMed Web of Science ®Google Scholar
• Olive KP, Jacobetz MA, Davidson CJ, et al. Inhibition of Hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer. Science 2009;324(5933):1457-61
   PubMed Web of Science ®Google Scholar
• Cheng XB, Sato N, Kohi S, Yamaguchi K. Prognostic impact of hyaluronan and its regulators in pancreatic ductal adenocarcinoma. PLoS One 2013;8(11):e80765
   PubMed Web of Science ®Google Scholar
• Toole BP, Slomiany MG. Hyaluronan: a constitutive regulator of chemoresistance and malignancy in cancer cells. Semin Cancer Biol 2008;18(4):244-50
   PubMed Web of Science ®Google Scholar
• Arpicco S, Lerda C, Dalla Pozza E, et al. Hyaluronic acid-coated liposomes for active targeting of gemcitabine. Eur J Pharm Biopharm 2013;85(3):373-80
   PubMed Web of Science ®Google Scholar
• Thompson CB, Shepard HM, O'Connor PM, et al. Enzymatic depletion of tumor hyaluronan induces antitumor responses in preclinical animal models. Mol Cancer Ther 2010;9(11):3052-64
   PubMed Web of Science ®Google Scholar
• Provenzano PP, Cuevas C, Chang AE, et al. Enzymatic targeting of the stroma ablates physical barriers to treatment of pancreatic ductal adenocarcinoma. Cancer Cell 2012;21(3):418-29
   PubMed Web of Science ®Google Scholar
• Jacobetz MA, Chan DS, Neesse A, et al. Hyaluronan impairs vascular function and drug delivery in a mouse model of pancreatic cancer. Gut 2013;62(1):112-20
   PubMed Web of Science ®Google Scholar
• Hingorani SR, Harris WP, Beck JT, et al. A phase Ib study of gemcitabine plus PEGPH20 (pegylated recombinant human hyaluronidase) in patients with stage IV previously untreated pancreatic cancer. J Clin Oncol 2013;31(Suppl):abstract #4010
   Google Scholar
• Mazar AP, Ahn RW, O'Halloran TV. Development of novel therapeutics targeting the urokinase plasminogen activator receptor (uPAR) and their translation toward the clinic. Curr Pharm Des 2011;17(19):1970-8
   PubMed Web of Science ®Google Scholar
• Laufs S, Schumacher J, Allgayer H. Urokinase-receptor (u-PAR) an essential player in multiple games of cancer: a review on its role in tumour progression, invasion, metastasis, proliferation/dormancy, clinical outcome and minimal residual disease. Cell Cycle 2006;5:1760-71
   PubMed Web of Science ®Google Scholar
• Xue A, Scarlett CJ, Jackson CJ, et al. Prognostic significance of growth factors and the urokinase-type plasminogen activator system in pancreatic ductal adenocarcinoma. Pancreas 2008;36(2):160-7
   PubMed Web of Science ®Google Scholar
• Hildenbrand R, Gandhari M, Stroebel P, et al. The urokinase-system--role of cell proliferation and apoptosis. Histol Histopathol 2008;23(2):227-36
   PubMed Web of Science ®Google Scholar
• Gorantla B, Asuthkar S, Rao JS, et al. Suppression of the uPAR-uPA system retards angiogenesis, invasion, and in vivo tumor development in pancreatic cancer cells. Mol Cancer Res 2011;9(4):377-89
   PubMed Web of Science ®Google Scholar
• Asuthkar S, Stepanova V, Lebedeva T, et al. Multifunctional roles of urokinase plasminogen activator (uPA) in cancer stemness and chemoresistance of pancreatic cancer. Mol Biol Cell 2013;24(17):2620-32
   PubMed Web of Science ®Google Scholar
• Heinemann V, Ebert MP, Laubender RP, et al. Phase II randomized proof-of-concept study of the urokinase inhibitor upamostat (WX-671) in combination with gemcitabine compared with gemcitabine alone in patients with non-resectable, locally advanced pancreatic cancer. Br J Cancer 2013;108(4):766-70
   PubMed Web of Science ®Google Scholar
• Abel EV, Simeone DM. Biology and clinical applications of pancreatic cancer stem cells. Gastroenterology 2013;144(6):1241-8
   PubMed Web of Science ®Google Scholar
• Gherardi E, Birchmeier W, Birchmeier C, Vande Woude G. Targeting MET in cancer: rationale and progress. Nat Rev Cancer 2012;12(2):89-103
   PubMed Web of Science ®Google Scholar
• Scagliotti GV, Novello S, von Pawel J. The emerging role of MET/HGF inhibitors in oncology. Cancer Treat Rev 2013;39(7):793-801
   PubMed Web of Science ®Google Scholar
• Hage C, Rausch V, Giese N, et al. The novel c-Met inhibitor cabozantinib overcomes gemcitabine resistance and stem cell signaling in pancreatic cancer. Cell Death Dis 2013;4:e627
   PubMed Web of Science ®Google Scholar
• Gandhi L, Jänne PA. Crizotinib for ALK-rearranged non-small cell lung cancer: a new targeted therapy for a new target. Clin Cancer Res 2012;18(14):3737-42
   PubMed Web of Science ®Google Scholar
• Avan A, Caretti V, Funel N, et al. Crizotinib inhibits metabolic inactivation of gemcitabine in c-Met-driven pancreatic carcinoma. Cancer Res 2013;73(22):6745-56
   PubMed Web of Science ®Google Scholar
• Yoshida T, Endo Y, Obata T, et al. Influence of cytidine deaminase on antitumor activity of 2'-deoxycytidine analogs in vitro and in vivo. Drug Metab Dispos 2010;38(10):1814-19
   PubMed Web of Science ®Google Scholar
• Frese KK, Neesse A, Cook N, et al. nab-Paclitaxel potentiates gemcitabine activity by reducing cytidine deaminase levels in a mouse model of pancreatic cancer. Cancer Discov 2012;2(3):260-9
   PubMed Web of Science ®Google Scholar
• Gómez-Quiroz LE, Factor VM, Kaposi-Novak P, et al. Hepatocyte-specific c-Met deletion disrupts redox homeostasis and sensitizes to Fas-mediated apoptosis. J Biol Chem 2008;283(21):14581-9
   PubMed Web of Science ®Google Scholar
• Mars WM, Zarnegar R, Michalopoulos GK. Activation of hepatocyte growth factor by the plasminogen activators uPA and tPA. Am J Pathol 1993;143(3):949-58
   PubMed Web of Science ®Google Scholar
• Birchmeier C, Gherardi E. Developmental roles of HGF/SF and its receptor, the c-Met tyrosine kinase. Trends Cell Biol 1998;8(10):404-10
   PubMed Web of Science ®Google Scholar
• Owen KA, Qiu D, Alves J, et al. Pericellular activation of hepatocyte growth factor by the transmembrane serine proteases matriptase and hepsin, but not by the membrane-associated protease uPA. Biochem J 2010;426(2):219-28
   PubMed Web of Science ®Google Scholar
• Sisson TH, Nguyen MH, Yu B, et al. Urokinase-type plasminogen activator increases hepatocyte growth factor activity required for skeletal muscle regeneration. Blood 2009;114(24):5052-61
   PubMed Web of Science ®Google Scholar
• Shanmukhappa K, Matte U, Degen JL, Bezerra JA. Plasmin-mediated proteolysis is required for hepatocyte growth factor activation during liver repair. J Biol Chem 2009;284(19):12917-23
   PubMed Web of Science ®Google Scholar
• Cebola I, Peinado MA. Epigenetic deregulation of the COX pathway in cancer. Prog Lipid Res 2012;51(4):301-13
   PubMed Web of Science ®Google Scholar
• Matsubayashi H, Infante JR, Winter J, et al. Tumor COX-2 expression and prognosis of patients with resectable pancreatic cancer. Cancer Biol Ther 2007;6:1569-75
   PubMed Web of Science ®Google Scholar
• Wang D, Dubois RN. Prostaglandins and cancer. Gut 2006;55(1):115-22
   PubMed Web of Science ®Google Scholar
• Philip B, Roland CL, Daniluk J, et al. a high-fat diet activates oncogenic Kras and COX2 to induce development of pancreatic ductal adenocarcinoma in mice. Gastroenterology 2013;145(6):1449-58
   PubMed Web of Science ®Google Scholar
• Li W, Mao Z, Fan X, et al. Cyclooxygenase 2 promoted the tumorigenecity of pancreatic cancer cells. Tumour Biol 2013. [Epub ahead of print]
   Web of Science ®Google Scholar
• Dragovich T, Burris H III, Loehrer P, et al. Gemcitabine plus celecoxib in patients with advanced or metastatic pancreatic adenocarcinoma: results of a phase II trial. Am J Clin Oncol 2008;31(2):157-62
   PubMed Web of Science ®Google Scholar
• Lipton A, Campbell-Baird C, Witters L, et al. Phase II trial of gemcitabine, irinotecan, and celecoxib in patients with advanced pancreatic cancer. J Clin Gastroenterol 2010;44(4):286-8
   PubMed Web of Science ®Google Scholar
• Kirane A, Toombs JE, Ostapoff K, et al. Apricoxib, a novel inhibitor of COX-2, markedly improves standard therapy response in molecularly defined models of pancreatic cancer. Clin Cancer Res 2012;18(18):5031-42
   PubMed Web of Science ®Google Scholar
• Kirane A, Toombs JE, Larsen JE, et al. Epithelial-mesenchymal transition increases tumor sensitivity to COX-2 inhibition by apricoxib. Carcinogenesis 2012;33(9):1639-46
   PubMed Web of Science ®Google Scholar
• Tsai JH, Yang J. Epithelial-mesenchymal plasticity in carcinoma metastasis. Genes Dev 2013;27(20):2192-206
   PubMed Web of Science ®Google Scholar
• Gasperowicz M, Rai A, Cross JC. Spatiotemporal expression of notch receptors and ligands in developing mouse placenta. Gene Expr Patterns 2013;13(7):249-54
   PubMed Web of Science ®Google Scholar
• Mizuma M, Rasheed ZA, Yabuuchi S, et al. The gamma secretase inhibitor MRK-003 attenuates pancreatic cancer growth in preclinical models. Mol Cancer Ther 2012;11(9):1999-2009
   PubMed Web of Science ®Google Scholar
• Hu H, Zhou L, Awadallah A, Xin W. Significance of notch1-signaling pathway in human pancreatic development and carcinogenesis. Appl Immunohistochem Mol Morphol 2013;21(3):242-7
   PubMedGoogle Scholar
• Hanlon L, Avila JL, Demarest RM, et al. Notch1 functions as a tumor suppressor in a model of K-ras-induced pancreatic ductal adenocarcinoma. Cancer Res 2010;70(11):4280-6
   PubMed Web of Science ®Google Scholar
• Murtaugh LC, Stanger BZ, Kwan KM, Melton DA. Notch signaling controls multiple steps of pancreatic differentiation. Proc Natl Acad Sci USA 2003;100(25):14920-5
   PubMed Web of Science ®Google Scholar
• Bao B, Wang Z, Ali S, et al. Notch-1 induces epithelial-mesenchymal transition consistent with cancer stem cell phenotype in pancreatic cancer cells. Cancer Lett 2011;1;307(1):26-36
   PubMed Web of Science ®Google Scholar
• Sundaram MV. The love-hate relationship between Ras and notch. Genes Dev 2005;19(16):1825-39
   PubMed Web of Science ®Google Scholar
• Golde TE, Koo EH, Felsenstein KM, et al. Gamma-secretase inhibitors and modulators. Biochim Biophys Acta 2013;1828(12):2898-907
   PubMed Web of Science ®Google Scholar
• Cook N, Frese KK, Bapiro TE, et al. Gamma secretase inhibition promotes hypoxic necrosis in mouse pancreatic ductal adenocarcinoma. J Exp Med 2012;209(3):437-44
   PubMed Web of Science ®Google Scholar
• Yabuuchi S, Pai SG, Campbell NR, et al. Notch signaling pathway targeted therapy suppresses tumor progression and metastatic spread in pancreatic cancer. Cancer Lett 2013;335(1):41-51
   PubMed Web of Science ®Google Scholar
• Krop I, Demuth T, Guthrie T, et al. Phase I pharmacologic and pharmacodynamic study of the gamma secretase (notch) inhibitor MK-0752 in adult patients with advanced solid tumors. J Clin Oncol 2012;30(19):2307-13
   PubMed Web of Science ®Google Scholar
• Doody RS, Raman R, Farlow M, Alzheimer's Disease Cooperative Study Steering Committee Semagacestat Study Group. A phase 3 trial of semagacestat for treatment of alzheimer's disease. N Engl J Med 2013;369(4):341-50
   PubMed Web of Science ®Google Scholar
• Wei P, Walls M, Qiu M, et al. Evaluation of selective gamma-secretase inhibitor PF-03084014 for its antitumor efficacy and gastrointestinal safety to guide optimal clinical trial design. Mol Cancer Ther 2010;9(6):1618-28
   PubMed Web of Science ®Google Scholar
• Wu Y, Cain-Hom C, Choy L, et al. Therapeutic antibody targeting of individual notch receptors. Nature 2010;464(7291):1052-7
   PubMed Web of Science ®Google Scholar
• Takebe N, Nguyen D, Yang SX. Targeting notch signaling pathway in cancer: clinical development advances and challenges. Pharmacol Ther 2014;Feb;141(2):140-9
   PubMed Web of Science ®Google Scholar
• Liu Z, Fan F, Wang A, et al. Dll4-notch signaling in regulation of tumor angiogenesis. J Cancer Res Clin Oncol 2014;Apr;140(4):525-36
   PubMed Web of Science ®Google Scholar
• Koutsounas I, Giaginis C, Theocharis S. Histone deacetylase inhibitors and pancreatic cancer: are there any promising clinical trials? World J Gastroenterol 2013;19(8):1173-81
   PubMed Web of Science ®Google Scholar
• Bojang P Jr, Ramos KS. The promise and failures of epigenetic therapies for cancer treatment. Cancer Treat Rev 2014;40(1):153-69
   PubMed Web of Science ®Google Scholar
• Kim HJ, Bae SC. Histone deacetylase inhibitors: molecular mechanisms of action and clinical trials as anti-cancer drugs. Am J Transl Res 2011;3(2):166-79
   PubMed Web of Science ®Google Scholar
• Glozak MA, Sengupta N, Zhang X, Seto E. Acetylation and deacetylation of non-histone proteins. Gene 2005;363:15-23
   PubMed Web of Science ®Google Scholar
• Yee NS, Zhou W, Chun SG, et al. Targeting developmental regulators of zebrafish exocrine pancreas as a therapeutic approach in human pancreatic cancer. Biol Open 2012;1(4):295-307
   Google Scholar
• Peulen O, Gonzalez A, Peixoto P, et al. The anti-tumor effect of HDAC inhibition in a human pancreas cancer model is significantly improved by the simultaneous inhibition of cyclooxygenase 2. PLoS One 2013;8(9):e75102
   PubMed Web of Science ®Google Scholar
• Marshall L, White RJ. Non-coding RNA production by RNA polymerase III is implicated in cancer. Nat Rev Cancer 2008;8(12):911-14
   PubMed Web of Science ®Google Scholar
• Wang X, Li G, Wang A, et al. Combined histone deacetylase and cyclooxygenase inhibition achieves enhanced antiangiogenic effects in lung cancer cells. Mol Carcinog 2013;52(3):218-28
   PubMed Web of Science ®Google Scholar
• SEER Stat Fact Sheets: pancreas Cancer. National Cancer Institute. Ed. Institute, N.C. Available from: http://seercancergov/statfacts/html/pancreas.html [Last Accessed 3 December 2013]
   Google Scholar
• Cancer Facts & Figures 2013. American Cancer Society (American Cancer Society, Atlanta; 2013).
   Google Scholar