参考文献
［1］ Chang MC，Wong JM，Chang YT.Screening and early detection of pancreatic cancer in high risk population［J］.World Journal of Gastroenterology，2014，20（9）：2358-2364.
［2］ Khan MA，Azim S，Zubair H，et al.Molecular drivers of pancreatic cancer pathogenesis：looking inward to move forward［J］.International journal of molecular sciences，2017，18（4）.
［3］ Poruk KE，Firpo MA，Adler DG，et al.Screening for pancreatic cancer：why，how，and who？［J］.Annals of surgery，2013，257（1）：17-26.
［4］ Ceyhan GO，Friess H.Pancreatic disease in 2014：pancreatic fibrosis and standard diagnostics［J］.Nat Rev Gastroenterol Hepatol，2015，12（2）：68-70.
［5］ Adamek HE，Albert J，Breer H，et al.Pancreatic cancer detection with magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography：aprospective controlled study［J］.Lancet（London，England），2000，356（9225）：190-193.
［6］ Petrone MC，Arcidiacono PG.New strategies for the early detection of pancreatic cancer［J］.Expert review of gastroenterology &hepatology，2016，10（2）：157-159.
［7］ Hanada K，Okazaki A，Hirano N，et al.Effective screening for early diagnosis of pancreatic cancer，best practice &research［J］.Clinical gastroenterology，2015，29（6）：929-939.
［8］ Tanaka K，Kida M.Role of endoscopy in screening of early pancreatic cancer and bile duct cancer［J］.Digestive Endoscopy Official Journal of the Japan Gastroenterological Endoscopy Society，2010，21（s1）：S97-S100.
［9］ Bilimoria KY，Bentrem DJ，Ko CY，et al.Multimodality therapy for pancreatic cancer in the U.S.：utilization，outcomes，and the effect of hospital volume［J］.Cancer，2007，110（6）：1227-1234.
［10］ Lall CG，Howard TJ，Skandarajah A.New concepts in staging and treatment of locally advanced pancreatic head cancer［J］.American journal of roentgenology，2007，189（5）：1044-1050.
［11］ Neuzillet C，Tijeras-Raballand A，de Mestier L，et al.MEK in cancer and cancer therapy［J］.Pharmacology &therapeutics，2014，141（2）：160-171.
［12］ Matsuda K，Idezawa T，You XJ，et al.Multiple mitogenic pathways in pancreatic cancer cells are blocked by a truncated epidermal growth factor receptor［J］.Cancer research，2002，62（19）：5611-5617.
［13］ Perugini RA，McDade TP，Vittimberga FJ，et al.Pancreatic cancer cell proliferation is phosphatidylinositol 3-kinase dependent［J］.The Journal of Surgical Research，2000，90（1）：39-44.
［14］ Cheng JQ，Ruggeri B，Klein WM，et al.Amplification of AKT2in human pancreatic cells and inhibition of AKT2expression and tumorigenicity by antisense RNA［J］.Proceedings of the National Academy of Sciences of the United States of America，1996，93（8）：3636-3641.
［15］ Tobita K，Kijima H，Dowaki S，et al.Epidermal growth factor receptor expression in human pancreatic cancer：significance for liver metastasis［J］.International Journal of Molecular Medicine，2003，11（3）：305-309.
［16］ Chio IIC，Jafarnejad SM，Ponz-Sarvise M，et al.NRF2promotes tumor maintenance by modulating mRNA translation in pancreatic cancer［J］.Cell，2016，166（4）：963-976.
［17］ Singla，Smit.Dual ErbB1and ErbB2receptor tyrosine kinase inhibition exerts synergistic effect with conventional chemotherapy in pancreatic cancer［J］.Oncology Reports，2012，28（6）：2211-2216.
［18］ Dragovich T，Laheru D，Dayyani F，et al.PhaseⅡtrial of vatalanib in patients with advanced or metastatic pancreatic adenocarcinoma after first-line gemcitabine therapy（PCRT O4-001）［J］.Cancer Chemotherapy and Pharmacology，2014，74（2）：379-387.
［19］ Demyanets S，Kaun C，Rychli K，et al.Oncostatin M-enhanced vascular endothelial growth factor expression in human vascular smooth muscle cells involves PI3K-，p38MAPK-，Erk1／2-and STAT1／STAT3-dependent pathways and is attenuated by interferon-γ［J］.Basic Research in Cardiology，2011，106（2）：217-231.
［20］ Marine G，Ezequiel C，Ana A，et al.Pancreatic cancer-induced cachexia is Jak2-dependent in mice［J］.Journal of Cellular Physiology，2015，229（10）：1437-1443.
［21］ Zhang M，Sun C，Shan X，et al.Inhibition of pancreatic cancer cell growth by cucurbitacin B through modulation of signal transducer and activator of transcription 3signaling［J］.Pancreas，2010，39（6）：923-929.
［22］ Kobayashi S，Kishimoto T，Kamata S，et al.Rapamycin，a specific inhibitor of the mammalian target of rapamycin，suppresses lymphangiogenesis and lymphatic metastasis［J］.Cancer science，2007，98（5）：726-733.
［23］ Dai ZJ，Gao，Kang，et al.Targeted inhibition of mammalian target of rapamycin（mTOR）enhances radiosensitivity in pancreatic carcinoma cells［J］.Drug Design Development and Therapy，2013：149-159.
［24］ Manegold PC，Paringer C，Kulka U，et al.Antiangiogenic therapy with mammalian target of rapamycin inhibitor RAD001（Everolimus）increases radiosensitivity in solid cancer［J］.Clinical Cancer Research，2008，14（3）：892-900.
［25］ Chen J，Zhao KN，Li R，et al.Activation of PI3K／Akt／mTOR pathway and dual inhibitors of PI3K and mTOR in endometrial cancer［J］.Current Medicinal Chemistry，2014，21（26）：3070-3080.
［26］ Deryugina EI，Quigley JP.Tumor angiogenesis：MMP-mediated induction of intravasation and metastasis-sustaining neovasculature［J］.Matrix Biology，2015，44-46：94-112.
［27］ Casey SC，Amedei A，Aquilano K，et al.Cancer prevention and therapy through the modulation of the tumor microenvironment［J］.Seminars in Cancer Biology，2015，35：S1044579X15000152.
［28］ Marschall ZV，Cramer T，Höcker M，et al.De novo expression of vascular endothelial growth factor in human pancreatic cancer：evidence for an autocrine mitogenic loop［J］.Gastroenterology，2000，119（5）：1358-1372.
［29］ Masood R.Vascular endothelial growth factor（VEGF）is an autocrine growth factor for VEGF receptor-positive human tumors［J］.Blood，2001，98（6）：1904-1913.
［30］ Samuel N，Hudson TJ.The molecular and cellular heterogeneity of pancreatic ductal adenocarcinoma［J］.Nature Reviews Gastroenterology &Hepatology，2011，9（2）：77-87.
［31］ Van Cutsem E，Vervenne WL，Bennouna J，et al.PhaseⅢtrial of bevacizumab in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer［J］.Journal of Clinical Oncology，2009，27（13）：2231-2237.
［32］ Watkins DJ，Starling N，Cunningham D，et al.The combination of a chemotherapy doublet（gemcitabine and capecitabine）with a biological doublet（bevacizumab and erlotinib）in patients with advanced pancreatic adenocarcinoma［J］.European Journal of Cancer，2014，50（8）：1422-1429.
［33］ Spano JP，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 phaseⅡstudy［J］.Lancet，2008，371（9630）：2101-2108.(https://www.daowen.com)
［34］ Rougier P，Riess H，Manges R，et al.Randomised，placebo-controlled，double-blind，parallel-group phaseⅢstudy evaluating aflibercept in patients receiving first-line treatment with gemcitabine for metastatic pancreatic cancer［J］.European Journal of Cancer，2013，49（12）：2633-2642.
［35］ Taeger J，Moser C，Hellerbrand C，et al.Targeting FGFR／PDGFR／VEGFR impairs tumor growth，angiogenesis，and metastasis by effects on tumor cells，endothelial cells，and pericytes in pancreatic cancer［J］.Molecular Cancer Therapeutics，2011，10（11）：2157-2167.
［36］ Goncalves A，Gilabert M，Francois E，et al.BAYPAN study：a double-blind phaseⅢrandomized trial comparing gemcitabine plus sorafenib and gemcitabine plus placebo in patients with advanced pancreatic cancer［J］.Annals of Oncology，2012，23（11）：2799-2805.
［37］ O'Reilly MS，Boehm T，Shing Y，et al.Endostatin：an endogenous inhibitor of angiogenesis and tumor growth［J］.Cell，1997，88（2）：277-285.
［38］ Ye W，Liu R，Pan C，et al.Multicenter randomized phase 2clinical trial of a recombinant human endostatin adenovirus in patients with advanced head and neck carcinoma［J］.Molecular Therapy，2014，22（6）：1221-1229.
［39］ Kulke，MH.PhaseⅡstudy of recombinant human endostatin in patients with advanced neuroendocrine tumors［J］.Journal of Clinical Oncology，2006，24（22）：3555-3561.
［40］ Guo J，Gao J，Li Z，et al.Adenovirus vector-mediated Gli1siRNA induces growth inhibition and apoptosis in human pancreatic cancer with Smo-dependent or Smo-independent Hh pathway activation in vitro and in vivo［J］.Cancer Letters，2013，339（2）：185-194.
［41］ Singh BN，Fu J，Srivastava RK，et al.Hedgehog signaling antagonist GDC-0449（Vismodegib）inhibits pancreatic cancer stem cell characteristics：molecular mechanisms［J］.PLoS ONE，2011，6（11）：e27306.
［42］ Ma WW，Messersmith WA，Dy GK，et al.PhaseⅠstudy of Rigosertib，an inhibitor of the phosphatidylinositol 3-kinase and Polo-like kinase 1pathways，combined with gemcitabine in patients with solid tumors and pancreatic cancer［J］.Clinical Cancer Research，2012，18（7）：2048.
［43］ Ding N，Cui XX，Gao Z，et al.A triple combination of atorvastatin，celecoxib and tipifarnib strongly inhibits pancreatic cancer cells and xenograft pancreatic tumors［J］.International Journal of Oncology，2014，44（6）：2139-2145.
［44］ Chitkara D，Mittal A，Mahato RI.MiRNAs in pancreatic cancer：therapeutic potential，delivery challenges and strategies［J］.Advanced Drug Delivery Reviews，2015，81：34-52.
［45］ Feng H，Wang Y，Su J，et al.MicroRNA-148asuppresses the proliferation and migration of pancreatic cancer cells by down-regulating ErbB3［J］.Pancreas，2016，45（9）：1263.
［46］ Ji Q，Hao X，Zhang M，et al.MicroRNA miR-34inhibits human pancreatic cancer tumor-initiating cells［J］.PLOS ONE，2009，4（8）：e6816.
［47］ Habbe N，Koorstra JBM，Mendell JT，et al.MicroRNA miR-155is a biomarker of early pancreatic neoplasia［J］.Cancer Biology &Therapy，2009，8（4）：340-346.
［48］ Frampton AE，Castellano L，Colombo T，et al.Integrated molecular analysis to investigate the role of microRNAs in pancreatic tumour growth and progression［J］.The Lancet，2015，385：S37.
［49］ Dillhoff M，Liu J，Frankel W，et al.MicroRNA-21is overexpressed in pancreatic cancer and a potential predictor of survival［J］.Journal of gastrointestinal surgery，2008，12（12）：2171-2176.
［50］ Hwang JH，Voortman J，Giovannetti E，et al.Identification of MicroRNA-21as a biomarker for chemoresistance and clinical outcome following adjuvant therapy in resectable pancreatic cancer［J］.PLOS ONE，2010，5（5）：e10630.
［51］ Sarkar S，Dubaybo H，Ali S，et al.Down-regulation of miR-221inhibits proliferation of pancreatic cancer cells through up-regulation of PTEN，p27（kip1），p57（kip2），and PUMA［J］.American Journal of Cancer Research，2013，3（5）：465-477.
［52］ Park JK，Lee EJ，Esau C，et al.Antisense inhibition of microRNA-21or-221arrests cell cycle，induces apoptosis，and sensitizes the effects of gemcitabine in pancreatic adenocarcinoma［J］.Pancreas，2009，38（7）：e190-e199.
［53］ Ma C，Nong K，Wu B，et al.MiR-212promotes pancreatic cancer cell growth and invasion by targeting the hedgehog signaling pathway receptor patched-1［J］.Journal of Experimental &Clinical Cancer Research，2014，33（1）：54.
［54］ Ma J.Notch signaling pathway in pancreatic cancer progression［J］.Pancreatic Disorders and Therapy，2013，03（02）.
［55］ Ristorcelli E，Lombardo D.Targeting notch signaling in pancreatic cancer［J］.Expert Opinion on Therapeutic Targets，2010，14（5）：541-552.
［56］ Dara N，Su-Ni T，Marianna R，et al.Targeting epigenetic regulation of miR-34afor treatment of pancreatic cancer by inhibition of pancreatic cancer stem cells［J］.PLoS ONE，2011，6（8）：e24099.
［57］ Lazennec G，Lam PY.Recent discoveries concerning the tumor—mesenchymal stem cell interactions［J］.Biochimica et Biophysica Acta（BBA）—Reviews on Cancer，2016，1866（2）：290-299.
［58］ Guo S，Xu X，Tang Y，et al.MiR-15ainhibits cell proliferation and epithelial to mesenchymal transition in pancreatic ductal adenocarcinoma by down-regulating Bmi-1expression［J］.Cancer Letters，2014，344（1）：40-46.
［59］ Deng S，Zhu S，Wang B，et al.Chronic pancreatitis and pancreatic cancer demonstrate active epithelial—mesenchymal transition profile，regulated by miR-217-SIRT1pathway［J］.Cancer Letters，2014，355（2）：184-191.
［60］ Sun XJ，Liu BY，Yan S，et al.MicroRNA-29apromotes pancreatic cancer growth by inhibiting tristetraprolin［J］.Cellular physiology and biochemistry，2015，37（2）：707-718.
［61］ Listing H，Mardin WA，Wohlfromm S，et al.MiR-23a／-24-induced gene silencing results in mesothelial cell integration of pancreatic cancer［J］.British Journal of Cancer，2015，112（1）：131-139.
［62］ Moore MJ，Goldstein D，Hamm J，et al.National cancer institute of canada clinical trials，erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer：aphaseⅢtrial of the national cancer institute of canada clinical trials group［J］.Journal of clinical oncology，2007，25（15）：1960-1966.
［63］ Kindler HL，Richards DA，Garbo LE，et al.A randomized，placebo-controlled phase 2study of ganitumab（AMG 479）or conatumumab（AMG 655）in combination with gemcitabine in patients with metastatic pancreatic cancer［J］.Annals of Oncology，2012，23（11）：2834-2842.
［64］ Kindler HL，Niedzwiecki D，Hollis D，et al.Gemcitabine plus bevacizumab compared with gemcitabine plus placebo in patients with advanced pancreatic cancer：phaseⅢtrial of the cancer and leukemia group B（CALGB 80303）［J］.Journal of Clinical Oncology，2010，28（22）：3617-3622.
［65］ Kindler HL，Ioka T，Richel DJ，et al.Axitinib plus gemcitabine versus placebo plus gemcitabine in patients with advanced pancreatic adenocarcinoma：a double-blind randomised phase 3study［J］.Lancet Oncology，2011，12（3）：256-262.