NCT Research

CCRP Pancreas

Summary

The European Pancreas Center (EPC) of the Department of Surgery is one of the largest centers for pancreatic surgery in the world (750 pancreatic operations in 2016). Core research areas include surgical techniques, adjuvant therapy, immunotherapy and molecular disease mechanisms. Patients with inoperable disease are treated in the Department of Medical Oncology at the National Center for Tumor Diseases, which has a focus on innovative immunotherapy trials.

CCRP Pancreatic Cancer
 

Patients with an unusual young age or rare histology are included in the NCT MASTER program to characterize their tumors in detail and identify molecular targets for individualized therapies. The Department of Radiotherapy offers all modern radiotherapy approaches for patients with locally advanced cancer and symptomatic metastases and studies the role of heavy ion radiation in pancreatic cancer. The interdisciplinary endoscopy center is specialized in palliation and management of pre- and postoperative complications.
Many different laboratories in the DKFZ, the European Pancreas Center, the Department of Pathology and the NCT focus on the molecular basis of pancreatic cancer. Many of these groups have joined in the BMBF-funded PANC-STRAT consortium that aims to decipher mechanisms of pancreatic carcinogenesis and drug resistance and develop individualized early clinical trials.

Members designated as Contact Persons

PD Dr. Dr. Springfeld
Medical Oncology

 
 
 

Prof. Dr. Büchler
Dept. of General, Visceral and Transplantation Surgery, Heidelberg University Hospital
European Pancreas Center

Prof. Dr. Dr. Debus
Dept. of RadioOncology, NCT/Heidelberg University Hospital

Prof. Dr. Diener

Study Center of the German Surgical Society, Heidelberg University Hospital

Prof. Dr. Eils
Division of Theoretical Bioinformatics, German Cancer Research Center

PD Dr. Felix
Proteomics/Biomarker, Dept. of Surgery, Heidelberg University Hospital

PD Dr. Fortunato
Cell and Tissue Cytometry, Dept. of Surgery, Heidelberg University Hospital

Dr. Giese

Integrative Oncology, Dept. of Surgery, Heidelberg University Hospital

Prof. Dr. Glimm
Research Group Applied Stem Cell Biology, Division of Translational Oncology, NCT/German Cancer Research Center

Prof. Dr. Hackert

Section for Pancreatic Surgery, Dept. of. General, Visceral and Transplantation Surgery, Heidelberg University Hospital
European Pancreas Center

Dr. Häfner
Dept. of RadioOncology, NCT/Heidelberg University Hospital

Prof. Dr. Herr
Molecular OncoSurgery, Dept. of. Surgery, Heidelberg University Hospital

Prof. Dr. Jäger, Dr. Halama
Dept. Of Medical Oncology, NCT/Heidelberg University Hospital

Prof. Dr. Kauczor
Dept. of Diagnostic and Interventional Radiology, Heidelberg University Hospital

PD Dr. Michalski
Inflammation and Pancreatic Carcinogenesis, Dept. of Surgery, Heidelberg University Hospital

Prof. Dr. Offringa
Section for Pancreatic Cancer Research, Dept. of. General, Visceral and Transplantation Surgery, Heidelberg University Hospital
European Pancreas Center
Division of Molecular Oncology of Gastrointestinal Tumors, German Cancer Research Center

Prof. Dr. Radeleff
Section for Interventional Radiology, Dept. of Diagnostic and Interventional Radiology, Heidelberg University Hospital

Prof. Dr. Ryschich
Microcirculation and Cell migration, Dept. of Surgery, Heidelberg University Hospital

Prof. Dr. Sauer, Dr. Schaible
Interdisciplinary Endoscopy Unit, Dept. of Surgery and Internal Medicine IV, Heidelberg University Hospital

Prof. Dr. Schirmacher, PD Dr. Bergmann, Dr. Gaida

Dept. of Pathology, Heidelberg University Hospital

Dr. Sprick
Experimental Oncology, German Cancer Research Center/HI-STEM

PD Dr. Dr. Springfeld, Dr. Berger
Dept. of Medical Oncology, NCT/Heidelberg University Hospital

Prof. Dr. Stremmel, Prof. Dr. Koschny
Section for Interventional Radiology, Dept. of. Diagnostic and Interventional Radiology, Heidelberg University Hospital

Prof. Dr. Strobel

Section for Pancreatic Cancer Research, Dept. of. General, Visceral and Transplantation Surgery, Heidelberg University Hospital
European Pancreas Center

Prof. Dr. Trumpp
Division of Stem Cells and Cancer, German Cancer Research Center/HI-STEM

Prof. Dr. Ulrich
Section for Surgical Oncology, Dept. of. General, Visceral and Transplantation Surgery, Heidelberg University Hospital

Prof. Dr. Ungerechts
Research Group Oncolytic Virotherapy, Dept. of Translational Oncology and Medical Oncology, NCT/German Cancer Research Center/Heidelberg University Hospital

Prof. Dr. von Kalle, Prof. Dr. Glimm, Prof. Dr. Fröhling, Dr. Heining

Division of Translational Oncology, NCT/German Cancer Research Center

Scientific Aims

  • Stratification of surgical, adjuvant, and systemic therapy (PANC-STRAT-Consortium).
  • Understand the role of the immune system and develop immunotherapy.
  • Development of radiotherapy, including heavy ion therapy.
  • Targeting of clonal dynamics in human pancreatic cancer.


Clinical Aims

  • Providing the best possible surgery for pancreatic cancer patients
  • Offering innovative clinical trials for patients in every clinical situation
  • Defining the role of heavy ion treatment in the neoadjuvant setting
  • Development of a biomarker-driven therapeutic stratification concept
  • Optimization of endoscopic therapy of postoperative insufficiencies after surgery for pancreatic cancer
  1. Neoptolemos JP, Palmer DH, Ghaneh P, Psarelli EE, Valle JW, Halloran CM, Faluyi O, O'Reilly DA, Cunningham D, Wadsley J, Darby S, Meyer T, Gillmore R, Anthoney A, Lind P, Glimelius B, Falk S, Izbicki JR, Middleton GW, Cummins S, Ross PJ, Wasan H, McDonald A, Crosby T, Ma YT, Patel K, Sherriff D, Soomal R, Borg D, Sothi S, Hammel P, Hackert T, Jackson R, Büchler MW; European Study Group for Pancreatic Cancer. Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial.
    Lancet. 2017; 389(10073):1011-1024. Impact factor (2015): 44.002
  2. Jandaghi P, Najafabadi HS, Bauer AS, Papadakis AI, Fassan M, Hall A, Monast A, von Knebel Doeberitz M, Neoptolemos JP, Costello E, Greenhalf W, Scarpa A, Sipos B, Auld D, Lathrop M, Park M, Büchler MW, Strobel O, Hackert T, Giese NA, Zogopoulos G, Sangwan V, Huang S, Riazalhosseini Y, Hoheisel JD. Expression of DRD2 Is Increased in Human Pancreatic Ductal Adenocarcinoma and Inhibitors Slow Tumor Growth in Mice.
    Gastroenterology. 2016 Dec;151(6):1218-1231. Impact factor (2015): 18.187
  3. 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.
    J Natl Cancer Inst. 2014 Jan;106(1):djt347. Impact Factor (2014): 12.583
  4. 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, 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.
    J Clin Oncol. 2014 Feb 20;32(6):504-12. Impact factor (2014): 18,428
  5. Noll, E. M., Eisen, C., Stenzinger, A., Espinet, E., Muckenhuber, A., Klein, C., Vogel, V., Klaus, B., Nadler, W., Rösli, C., Lutz, C., Kulke, M., Engelhardt, J., Zickgraf, F., Espinosa, O., Schlesner, M., Jiang, X., Kopp-Schneider, A., Neuhaus, P., Bahra, M., Sinn, B., Eils, R., Giese, N., Hackert, T., Strobel, O., Werner, J., Büchler, M. W., Weichert, W., Trumpp, A., Sprick, M. R. CYP3A5 mediates basal and acquired therapy resistance in different subtypes of pancreatic ductal adenocarcinoma.
    Nat Med. 2016 Feb; Advance Online Publication 8.2.2016: Impact factor (2014): 28.223
  6. Dietlein, F., Kalb, B., Jokic, M., Noll, E. M., Strong, A., Tharun, L., Ozretic, L., Kunstlinger, H., Kambartel, K., Randerath, W. J., Jungst, C., Schmitt, A., Torgovnick, A., Richters, A., Rauh, D., Siedek, F., Persigehl, T., Mauch, C., Bartkova, J., Bradley, A., Sprick, M. R., Trumpp, A., Rad, R., Saur, D., Bartek, J., Wolf, J., Buttner, R., Thomas, R. K., and Reinhardt, H. C. (2015). A Synergistic Interaction between Chk1- and MK2 Inhibitors in KRAS-Mutant Cancer.
    Cell 2015 162, 146-159. Impact factor (2014): 32.242
  7. Childs EJ, Mocci E, Campa D, Bracci PM, Gallinger S, Goggins M, Li D, Neale RE, Olson SH, Scelo G, Amundadottir LT, Bamlet WR, Bijlsma MF, Blackford A, Borges M, Brennan P, Brenner H, Bueno-de-Mesquita HB, Canzian F, Capurso G, Cavestro GM, Chaffee KG, Chanock SJ, Cleary SP, Cotterchio M, Foretova L, Fuchs C, Funel N, Gazouli M, Hassan M, Herman JM, Holcatova I, Holly EA, Hoover RN, Hung RJ, Janout V, Key TJ, Kupcinskas J, Kurtz RC, Landi S, Lu L, Malecka-Panas E, Mambrini A, Mohelnikova-Duchonova B, Neoptolemos JP, Oberg AL, Orlow I, Pasquali C, Pezzilli R, Rizzato C, Saldia A, Scarpa A, Stolzenberg-Solomon RZ, Strobel O, Tavano F, Vashist YK, Vodicka P, Wolpin BM, Yu H, Petersen GM, Risch HA, Klein AP. Common variation at 2p13.3, 3q29, 7p13 and 17q25.1 associated with  susceptibility to pancreatic cancer.
    Nat Genet. 2015 Aug;47(8):911-6. Impact factor (2014): 29.352
  8. Wolpin BM, Rizzato C, Kraft P, Kooperberg C, Petersen GM, Wang Z, Arslan AA, Beane-Freeman L, Bracci PM, Buring J, Canzian F, Duell EJ, Gallinger S, Giles GG, Goodman GE, Goodman PJ, Jacobs EJ, Kamineni A, Klein AP, Kolonel LN, Kulke MH, Li D, Malats N, Olson SH, Risch HA, Sesso HD, Visvanathan K, White E, Zheng W, Abnet CC, Albanes D, Andreotti G, Austin MA, Barfield R, Basso D, Berndt SI, Boutron-Ruault MC, Brotzman M, Büchler MW, Bueno-de-Mesquita HB, Bugert P, Burdette L, Campa D, Caporaso NE, Capurso G, Chung C, Cotterchio M, Costello E, Elena J, Funel N, Gaziano JM, Giese NA, Giovannucci EL, Goggins M, Gorman MJ, Gross M, Haiman CA, Hassan M, Helzlsouer KJ, Henderson BE, Holly EA, Hu N, Hunter DJ, Innocenti F, Jenab M, Kaaks R, Key TJ, Khaw KT, Klein EA, Kogevinas M, Krogh V, Kupcinskas J, Kurtz RC, LaCroix A, Landi MT, Landi S, Le Marchand L, Mambrini A, Mannisto S, Milne RL, Nakamura Y, Oberg AL, Owzar K, Patel AV, Peeters PH, Peters U, Pezzilli R, Piepoli A, Porta M, Real FX, Riboli E, Rothman N, Scarpa A, Shu XO, Silverman DT, Soucek P, Sund M, Talar-Wojnarowska R, Taylor PR, Theodoropoulos GE, Thornquist M, Tjønneland A, Tobias GS, Trichopoulos D, Vodicka P, Wactawski-Wende J, Wentzensen N, Wu C, Yu H, Yu K, Zeleniuch-Jacquotte A, Hoover R, Hartge P, Fuchs C, Chanock SJ, Stolzenberg-Solomon RS, Amundadottir LT. Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer.
    Nat Genet. 2014 Sep;46(9):994-1000. Impact factor (2014): 29.352
  9. Alam MS, Gaida MM, Bergmann F, Lasitschka F, Giese T, Giese NA, Hackert T, Hinz U, Hussain SP, Kozlov SV, Ashwell JD. Selective inhibition of the p38 alternative activation pathway in infiltrating T cells inhibits pancreatic cancer progression.
    Nat Med. 2015 Nov;21(11):1337-43. Impact factor (2014): 28.223
  10. Hartmann N, Giese NA, Giese T, Pöschke I, Offringa R, Werner J, Ryschich E. Prevailing role of contact guidance in intrastromal T-cell trapping in human pancreatic cancer.
    Clin Cancer Res. 2014 Jul 1;20(13):3422-33. Impact factor (2014):8,722

Clinical Activities

Multidisciplinary patient management

  • Standardized treatment according to regularly updated NCT SOPs Pancreatic Cancer
  • Weekly interdisciplinary tumor boards (Tuesday Surgical Tumor board, Thursday GI-Tumor board)


Specific Treatment Options

  • Re-certified high-volume center of excellence for pancreatic surgery (DGAV 2015-2018)
  • Specialized outpatient clinics in the Department of Surgery/European Pancreas Center and the NCT
  • High international reputation for pancreatic pathology
  • Radiooncology facility with innovative radiation approaches including heavy ion treatment
  • Interdisciplinary GI endoscopy unit (IEZ, Gastroenterology/Surgery)
  • Clinical trial centers at NCT, Dep. of Surgery, Dep. of Radiooncology, Diagnostic Trial Center at the Institute of Pathology
  • Study Center of the German Surgical Society (SDGC)
  • Establishment of the role of adjuvant chemotherapy in pancreatic cancer
  • Multiple contributions regarding the optimal surgical therapy of pancreatic cancer
  • Establishment of  the European Pancreas Center

Preclinical Activities

Established technologies

  • Immune cell quantification on whole slide sections
  • Protein Multiplex Analysis on Tissue Sections
  • Serum Antibody Analyses (TAAs)
  • Patient-derived subtype specific PDX and cell culture models of PDAC
  • Isolation and ex vivo expansion of tumor-infiltration T-cells (TILs) from tumor biopsies
  • TCR deep sequencing
  • Prediction of tumor-specific T-cell epitopes on basis of exome sequencing and RNA-Seq
  • Genetic mouse tumor models based on transgenic mouse strains and in vivo electroporation
  • ctDNA-based screening of liquid biopsies
  • Tumor-Stroma dissection and detailed quantification of immune cell subpopulations (MDSCs, Lymphocytes, NK cells, macrophages etc.)
  • Cytokine and Chemokine Quantification of different compartments
  • Autoantibody profiling and antibody profiling of corresponding sera
  • Large scale multidimensional data algorithm fusion software approach for the identification of clinical relevant subgroups
  • Identification of a novel mechanism for primary and secondary therapy resistance in PDAC (Noll et al. Nature Med. 2016)
  • Establishment of a bank of characterized PDX and cell line models for PDAC (Noll et al. Nature Med. 2016, Dietlein et al. Cell 2015, and unpublished)
  • Identification of markers for stratification of clinically relevant PDAC subtypes (Noll et al. Nature Med. 2016)
  • Establishment of a mouse model for measles virus oncolytic therapy (Bossow S et al.,   Cancer Gene Ther. 2011)