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4th EPC-TM net General Assembly (GA) meeting

The 4th General Assembly meeting took place on Mallorca, Spain on March 24-26, 2014.

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Ekkirala CR, Cappello P, Accolla R S, Romero I, Garrido C, Garcia-Lora AM, Novelli F. Class li Transactivator-Induced Mhc Class Ii Expression in Pancreatic Cancer Cells Leads to Tumor Rejection and a Specific Antitumor Memory Response. Pancreas. Oct 2014; 43(7):1066-72. doi: 10.1097/MPA.0000000000000160.

Valle JW, Palmer D, Jackson R, Cox T, Neoptolemos JP, Ghaneh P, Rawcliffe CL, Bassi C, Stocken DD,  Cunningham D, O’Reilly D, Goldstein D, Robinson BA, Karapetis C, Scarfe A, Lacaine F, Sand J, Izbicki JR , Mayerle J, Dervenis C, Oláh A, Butturini G, Lind PA, Middleton MR, Anthoney A, Sumpter K,   Carter R and  Büchler MW. Optimal Duration and Timing of Adjuvant Chemotherapy After Definitive Surgery for Ductal Adenocarcinoma of the Pancreas: Ongoing Lessons From the ESPAC-3 Study. Journal of Clinical Oncology, 2014 Jan 13. doi: 10.1200/JCO.2013.50.7657

Greenhalf W, Ghaneh P, Neoptolemos JP,Palmer DH, Cox TF, Lamb RF, Garner E, Campbell F, Mackey JR, Costello E, Moore MJ, Valle JW, McDonald AC, Carter R, Tebbutt NC, Goldstein D, Shannon J, Dervenis C, Glimelius B, Deakin M, Charnley RM, Lacaine F, Scarfe AG, Middleton MR, Anthoney A, Halloran CM, Mayerle J, Oláh A, Jackson R, Rawcliffe CL, Scarpa A, Bassi C, Büchler MW. European Study Group for Pancreatic Cancer. Pancreatic Cancer hENT1 Expression and Survival From Gemcitabine in Patients From the ESPAC-3 Trial. Journal of National Cancer Institute, 2014 Jan 1; 106(1). doi: 10.1093/jnci/djt347.



Flández M, Cendrowski J, Cañamero M, Salas A, del Pozo N, Schoonjans K, Real FX. Nr5a2 heterozygosity sensitizes to, and cooperates with, inflammation in KRasG12V-driven pancreatic tumorigenesis. Gut 2013; In press.

Neesse A, Krug S, Gress TM, Tuveson DA, Michl P. E merging concepts in pancreatic cancer medicine: targeting the tumor stroma. OncoTargets and Therapy. Dec 2013; 2014(7):33 – 43

Kühnemuth B, Mühlberg L, Schipper M, Griesmann H, Neesse A, Milosevic N, Wissniowski T, Buchholz M, Gress TM, Michl P. CUX1 modulates polarization of tumor-associated macrophages by antagonizing NF- κ B signaling. Oncogene. 2013 Dec 16. doi: 10.1038/onc.2013.530. [Epub ahead of print]

Milosevic N, Kühnemuth B, Mühlberg L, Ripka S, Griesmann H, Lölkes C, Buchholz M, Aust D, PilarskyC, Krug S, Gress TM, Michl P. Synthetic Lethality Screen Identifies RPS6KA2 as Modifier of Epidermal Growth Factor Receptor Activity in Pancreatic Cancer. Neoplasia. 12 December 2013; 15:1354–1362

Celesti G, Di Caro G, Bianchi P, Grizzi F, Marchesi F, Basso G, Rahal D, Delconte G, Catalano M, Cappello P, Roncalli M, Zerbi A, Montorsi M, Novelli F,Mantovani A, Allavena P, Malesci A, Laghi L. Early expression of the fractalkine receptor CX3CR1 in pancreatic carcinogenesis. Br J Cancer. 2013 Oct 29; 109(9):2424-33. doi: 10.1038/bjc.2013.565. Epub 2013 Oct 1.

Capello M, Cappello P, Linty FC, Chiarle R, Sperduti I, Novarino A, Salacone P, Mandili G, Naccarati A, Sacerdote C, Beghelli S, Bersani S, Barbi S, Bassi C, Scarpa A, Nisticò P, Giovarelli M, Vineis P, Milella M, Novelli F. Autoantibodies to Ezrin are an early sign of pancreatic cancer in humans and in genetically engineered mouse models. J Hematol Oncol. 2013 Sep 6; 6:67. doi:10.1186/1756-8722-6-67.

Amedei A, Niccolai E, Benagiano M, Della Bella C, Cianchi F, Bechi P, Taddei A, Bencini L, Farsi M, Cappello P, Prisco D, Novelli F, D'Elios MM. Ex vivo analysis of pancreatic cancer-infiltrating T lymphocytes reveals thatENO-specific Tregs accumulate in tumor tissue and inhibit Th1/Th17 effector cell functions. Cancer Immunol Immunother. 2013 Jul; 62(7):1249-60. doi: 10.1007/s00262-013-1429-3. Epub 2013 May 3.

Neesse A, Hahnenkamp A, Griesmann H, Buchholz M, Hahn SA, Maghnouj A, Fendrich V, Ring J, Sipos B, Tuveson DA, Bremer C, Gress TM, Michl P. Claudin-4-targeted optical imaging detects pancreatic cancer and its precursor lesions. Gut. 2013 Jul; 62(7):1034-43. doi: 10.1136/gutjnl-2012-302577. Epub 2012 Jun 7.

Cappello P, Novelli F. A self antigen reopens the games in pancreatic cancer. Oncoimmunology. 2013 Jun 1; 2(6):e24384. Epub 2013 May 10.

Zhou W, Capello M, Fredolini C, Racanicchi L, Dugnani E, Piemonti L, LiottaLA, Novelli F, Petricoin EF. Mass spectrometric analysis reveals O-methylation of pyruvate kinase from pancreatic cancer cells. Anal Bioanal Chem. 2013 May; 405(14):4937-43. doi: 10.1007/s00216-013-6880-7. Epub 2013 Mar 19.

Cappello P, Rolla S, Chiarle R, Principe M, Cavallo F, Perconti G, Feo S, Giovarelli M, Novelli F. Vaccination with ENO1 DNA prolongs survival of genetically engineered mice with pancreatic cancer. Gastroenterology. 2013 May; 144(5):1098-106. doi: 10.1053/j.gastro.2013.01.020. Epub 2013 Jan 16.

Ceruti P, Principe M, Capello M, Cappello P, Novelli F. Three are better than one: plasminogen receptors as cancer theranostic targets. Exp Hematol Oncol. 2013 Apr 17; 2(1):12. doi: 10.1186/2162-3619-2-12.

Bianco M, Aloisi A, Arima V, Capello M, Ferri-Borgogno S, Novelli F, LeporattiS, Rinaldi R. Quartz crystal microbalance with dissipation (QCM-D) as tool to exploit antigen-antibody interactions in pancreatic ductal adenocarcinomadetection. Biosens Bioelectron. 2013 Apr 15; 42:646-52. doi: 10.1016/j.bios

Chiriacò MS, Primiceri E, Monteduro AG, Bove A, Leporatti S, Capello M,Ferri-Borgogno S, Rinaldi R, Novelli F, Maruccio G. Towards pancreatic cancer diagnosis using EIS biochips. Lab Chip. 2013 Feb 21; 13(4):730-4. doi:10.1039/c2lc41127j.

Griesmann H, Ripka S, Pralle M, Ellenrieder V, Baumgart S, Buchholz M, Pilarsky C, Aust D, Gress TM, Michl P. WNT5A-NFAT signaling mediates resistance to apoptosis in pancreatic cancer. Neoplasia. 2013 Jan;15(1):11-22.

Martinelli P, Cañamero M, del Pozo N, Madriles F, Zapata A, Real FX. Gata6 is required for complete acinar differentiation and maintenance of the exocrine pancreas in adult mice. Gut 2013; 2013; 62:1481-1488.

Campos ML, Sánchez-Arévalo Lobo V, Rodolosse A, Gottardi CJ, Maffincini A, Beghelli S, Scardoni M, Bassi C, Scarpa A, Real FX. ICAT is a novel Ptf1a interactor that regulates pancreatic acinar differentiation and displays altered expression in tumors. Biochem J 2013; 451:395-405.



Michl P, Gress TM. Improving drug delivery to pancreatic cancer: breaching the stromal fortress by targeting hyaluronic acid. Gut. 2012 Oct;61(10):1377-9. doi: 10.1136/gutjnl-2012-302604.

Baraniskin A, Nöpel-Dünnebacke S, Ahrens M, Jensen SG, Zöllner H, Maghnouj A, Wos A, Mayerle J, Munding J, Kost D, Reinacher-Schick A, Liffers S, Schroers R, Chromik AM, Meyer HE, Uhl W, Klein-Scory S, Weiss FU, Stephan C, Schwarte-Waldhoff I, Lerch MM, Tannapfel A, Schmiegel W, Andersen CL, Hahn SA. Circulating U2 small nuclear RNA fragments as a novel diagnostic biomarker for pancreatic and colorectal adenocarcinoma. Int J Cancer. 2012. doi: 10.1002/ijc.27791. [Epub ahead of print]

Zhou W, Capello M, Fredolini C, Racanicchi L, Piemonti L, Liotta LA, Novelli F, Petricoin EF. MS analysis reveals O-methylation of L-lactate dehydrogenase from pancreatic ductal adenocarcinoma cells. Electrophoresis. 2012; 33(12):1850-4.

Neesse A, Hahnenkamp A, Griesmann H, Buchholz M, Hahn SA, Maghnouj A, Fendrich V, Ring J, Sipos B, Tuveson DA, Bremer C, Gress TM, Michl P. Claudin-4-targeted optical imaging detects pancreatic cancer and its precursor lesions. Gut 2012. [Epub ahead of print]

Vaccaro V, Gelibter A, Bria E, Iapicca P, Cappello P, Di Modugno F, Pino MS, Nuzzo C, Cognetti F, Novelli F, Nistico P, Milella M. Molecular and genetic bases of pancreatic cancer. Curr Drug Targets. 2012; 13(6):731-43.

Lonardo E, Frias-Aldeguer J, Hermann PC, Heeschen C. Pancreatic stellate cells form a niche for cancer stem cells and promote their self-renewal and invasiveness. Cell Cycle 2012; 11(7):1282-90.

Jacobetz MA, Chan DS, Neesse A, Bapiro TE, Cook N, Frese KK, Feig C, Nakagawa T, Caldwell ME, Zecchini HI, Lolkema MP, Jiang P, Kultti A, Thompson CB, Maneval DC, Jodrell DI, Frost GI, Shepard HM, Skepper JN, Tuveson DA. Hyaluronan impairs vascular function and drug delivery in a mouse model of pancreatic cancer. Gut 2012 [Epub ahead of print].

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(3):260-9.

Perseghin G, Calori G, Lattuada G, Ragogna F, Dugnani E, Garancini MP, Crosignani P, Villa M, Bosi E, Ruotolo G, Piemonti L. Insulin resistance/hyperinsulinemia and cancer mortality: the Cremona study at the 15th year of follow-up. Acta Diabetol. 2012. [Epub ahead of print]



Gopinathan A, Denicola GM, Frese KK, Cook N, Karreth FA, Mayerle J, Lerch MM, Reinheckel T, Tuveson DA. Cathepsin B promotes the progression of pancreatic ductal adenocarcinoma in mice. Gut 2011; 61(6):877-84.

Zhou W, Capello M, Fredolini C, Racanicchi L, Piemonti L, Liotta LA, Novelli F, Petricoin EF. Proteomic analysis reveals Warburg effect and anomalous metabolism of glutamine in pancreatic cancer cells. J Proteome Res. 2012;11(2):554-63. Epub 2011 Nov 17.

Aghdassi A, Sendler M, Guenther A, Mayerle J, Behn CO, Heidecke CD, Friess H, Büchler M, Evert M, Lerch MM, Weiss FU. Recruitment of histone deacetylases HDAC1 and HDAC2 by the transcriptional repressor ZEB1 downregulates E-cadherin expression in pancreatic cancer. Gut 2011; 61(3):439-48.

Lonardo E, Hermann PC, Mueller MT, Huber S, Balic A, Miranda-Lorenzo I, Zagorac S, Alcala S, Rodriguez-Arabaolaza I, Ramirez JC, Torres-Ruíz R, Garcia E, Hidalgo M, Cebrián DÁ, Heuchel R, Löhr M, Berger F, Bartenstein P, Aicher A, Heeschen C. Nodal/Activin signaling drives self-renewal and tumorigenicity of pancreatic cancer stem cells and provides a target for combined drug therapy. Cell Stem Cell. 2011; 9(5):433-46.

Nitsche C, Edderkaoui M, Moore RM, Eibl G, Kasahara N, Treger J, Grippo PJ, Mayerle J, Lerch MM, Gukovskaya AS. The phosphatase PHLPP1 regulates Akt2, promotes pancreatic cancer cell death, and inhibits tumor formation. Gastroenterology. 2012;142(2):377-87.e1-5. Epub 2011 Oct 29.

Pinho AV, Rooman I, Real FX. p53-dependent regulation of growth, epithelial-mesenchymal transition, and stemness in normal pancreatic epithelial cells. Cell Cycle 2011; 10:1312-1321.

Zhou W, Capello M, Fredolini C, Racanicchi L, Piemonti L, Liotta LA, Novelli F, Petricoin EF. Phosphoproteomic Analysis of Pancreatic Ductal Adenocarcinoma Cells Reveals Differential Phosphorylation of Cell Adhesion, Cell Junction and Structural Proteins. J Proteomics Bioinform 2011; 4(9):170-178.

Partecke LI, Sendler M, Kaeding A, Weiss FU, Mayerle J, Dummer A, Nguyen TD, Albers N, Speerforck S, Lerch MM, Heidecke CD, von Bernstorff W, Stier A. A syngeneic orthotopic murine model of pancreatic adenocarcinoma in the C57/BL6 mouse using the Panc02 and 6606PDA cell lines. Eur Surg Res. 2011; 47(2):98-107.

Zhou W, Capello M, Fredolini C, Piemonti L, Liotta LA, Novelli F, Petricoin EF. Proteomic analysis of pancreatic ductal adenocarcinoma cells reveals metabolic alterations. J Proteome Res. 2011; 10(4):1944-52. Epub 2011 Feb 28.

Capello M, Ferri-Borgogno S, Cappello P, Novelli F. α-Enolase: a promising therapeutic and diagnostic tumor target. FEBS J. 2011; 278(7):1064-74. Epub 2011 Feb 24.

  • European Organisation of Research and Treatment of Cancer (EORTC)
  • The European Registry of Hereditary Pancreatitis And Familial Pancreatic Cancer (Europac)
  • European Federation of Biotechnology (EFB)
  • European Science Foundation (ESF)
  • European Pancreatic Club (EPC)
  • Forschungsprojekt Familiäres Pankreaskarzinom (FAPACA)
  • The Sol Goldman Pancreatic Cancer Research Center, John Hopkins University, USA
  • MedlinePlus– Trusted Health Information for you - U.S. National Library of Medicine and National Institutes of Health (NIH) - Pancreatic Cancer, USA
  • The National Pancreas Foundation (NPF), USA
  • National Cancer Institute at the National Institutes of Health - Pancreatic Cancer, USA
  • Pancreatica – Confronting Pancreatic Cancer, USA
  • Wikipedia – Pancreatic Cancer

Many clinical partners within the consortium are specialists in both clinical care for pancreatic cancer patients and pancreatic cancer research. The ultimate goal of every research effort must be to improve the therapeutic options to treat pancreatic cancer and improve the prognosis of this disease.

For an overview on risk factors, development, diagnosis and current therapeutic modalities for pancreatic cancer, we refer to several publicly available websites:

  • Pancreatic Cancer Action Network (US):
  • Cancer Research UK:
  • Macmillan Cancer Support (UK):
  • Deutsche Krebshilfe (Germany):
  • Arbeitskreis der Pankreatektomierten (Germany):
  • Pankreaszentrum Hessen (Germany):

Pancreatic cancer is one of the most lethal human cancers with a five-year survival rate of less than 5%. Late presentation and a high level of resistance to chemotherapeutic drugs are among the major reasons for this dismal prognosis. The presence of the highest degree of desmoplasia among all solid tumours and the fact that chronic inflammatory pancreatic disease is associated with an increased risk for pancreatic cancer indicate that the tumour microenvironment is of particular importance for carcinogenesis in the pancreas.

Incidence & treatment

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most difficult cancers to treat. It is the commonest cancer affecting the exocrine pancreas.

  • In 2000, there were 217,000 new cases of pancreatic cancer and 213,000 deaths world wide and 60 139 new patients (10.4% of all digestive tract cancers) and 64 801 deaths in Europe
  • These figures indicate that, due to the fact that most patients will die within one year of diagnosis, incidence equals mortality.
  • Without active treatment, metastatic pancreatic cancer has a median survival of 3–5 months and 6–10 months for locally advanced disease, which increases to around 11–15 months with resectional surgery
  • The late presentation and aggressive tumour biology of this disease determine that only a minority (10–15%) of patients can undergo potentially curative resection.
  • Major advances in the past decade are based on a decrease in surgical mortality and morbidity through the development of specialist regional centres and a modest increase in survival due to the use of systemic chemotherapy
  • Currently, the therapeutic armamentarium for pancreatic cancer consists of conventional chemotherapeutic agents such as gemcitabine and 5-fluorouracil, which have been shown to offer a marginal survival benefit for patients with advanced disease
  • In the adjuvant setting, survival can be extended to a median of 20-22 months
  • Moreover, unlike other cancer entities such as colon cancer, molecular targeted therapies have so far largely failed to positively impact patient survival in pancreatic cancer


Failure of therapeutic approaches

  • A plenitude of chemotherapeutic agents and novel molecular targeted therapies addressing epithelial tumour cells, all showing antitumour activity in cell culture and mouse experiments, have failed to show significant effects in clinical pancreatic cancer trials.
  • Thus, it appears that therapeutic approaches targeting pancreatic tumour cells alone are unlikely to improve the prognosis of pancreatic cancer.


Importance of the tumour microenvironment

  • Evidence accumulated during recent years for multiple tumours has clearly demonstrated that the tumour microenvironment comprising stroma, blood vessels, infiltrating inflammatory cells and a variety of associated tissue cells are of paramount importance in regulating proliferating tumour cells including a subpopulation of cancer stem cells and thus determine tumour aggression and chemoresistance.
  • The presence of the highest degree of desmoplasia among all solid tumours and the fact that chronic inflammatory pancreatic disease is associated with an increased risk for pancreatic cancer in both human and mouse models indicate that the tumour microenvironment seems to be of particular importance for carcinogenesis in the pancreas.
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