Helmholtz Alliance Preclinical Comprehensive Cancer Center

Helmholtz Alliance – Preclinical Comprehensive Cancer Center

Mission of the PCCC
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The availability of advanced preclinical tumor models has emerged as one of the most rate-limiting factors for both, the advancement of basic tumor biology and translational oncology research. Therefore, the Helmholtz Association has established the Helmholtz Alliance Preclinical Comprehensive Cancer Center (PCCC) as a nationwide network for the development and validation of established and novel preclinical cancer models of superior quality, which truly mimic the natural course of human tumor initiation, growth and metastasis. Our mission is to translate discoveries into the clinic: from bench to bedside. Focusing on key issues of contemporary oncology research, such concerted effort holds great prospect to revolutionize current cancer research.

Latest News

2nd International Kloster Seeon Meeting on Mouse Models of Human Cancer
April 30 - May 3, 2016
Kloster Seeon, Germany
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Ma C, Kesarwala AH, Eggert T, Medina-Echeverz J, Kleiner DE, Jin P, Stroncek DF, Terabe M, Kapoor V, ElGindi M, Han M, Thornton AM, Zhang H, Egger M, Luo J, Felsher DW, McVicar DW, Weber A, Heikenwalder M, Greten TF. NAFLD causes selective CD4(+) T lymphocyte loss and promotes hepatocarcinogenesis. Nature 531:253-7, 2016
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Sunami Y, Ringelhan M, Kokai E, Lu M, O'Connor T, Lorentzen A, Weber A, Rodewald A-K, Müllhaupt B, Terracciano L, Gul S, Wissel S, Leithäuser F, Krappmann D, Riedl P, Hartmann D, Schirmbeck R, Strnad P, Hüser N, Kleeff J, Friess H, Schmid RM, Geisler F, Wirth T, Heikenwalder M: Canonical NF-κB signaling in hepatocytes acts as a tumor-suppressor in HBV surface antigen-driven HCC by controlling the UPR. Hepatology, 01 2016 E Pub ahead of print online.Accepted manuscript online: 11 JAN 2016
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Garnelo M, Tan A, Her Z, Yeong J, Lim CJ, Chen J, Lim KH, Weber A, Chow P, Chung A, Ooi LL, Toh HC, Heikenwalder M, Ng IO, Nardin A, Chen Q, Abastado JP, Chew V: Interaction between tumour-infiltrating B cells and T cells controls the progression of hepatocellular carcinoma. Gut. 2015 Dec 15. pii: gutjnl-2015-310814. doi: 10.1136/gutjnl-2015-310814. [Epub ahead of print]
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Weber J, Öllinger R, Friedrich M, Ehmer U, Barenboim M, Steiger K, Heid I, Mueller S, Maresch R, Engleitner T, Gross N, Geumann U, Fu B, Segler A, Yuan D, Lange S, Strong A, de la Rosa J, Esposito I, Liu P, Cadiñanos J, Vassiliou GS, Schmid RM, Schneider G, Unger K, Yang F, Braren R, Heikenwälder M, Varela I, Saur D, Bradley A, Rad R: CRISPR/Cas9 somatic multiplex-mutagenesis for high-throughput functional cancer genomics in mice. Proc Natl Acad Sci U S A. 112:13982-7, 2015
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Lemos C, Hardt MS, Juneja M, Voss C, Forster S, Jerchow B, Haider W, Blaker H, Stein U: MACC1 induces tumor progression in transgenic mice and colorectal cancer patients via increased pluripotency markers Nanog and Oct4. Clin Cancer Res. 2016, pii: clincanres.1425.2015. [Epub ahead of print]  
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Knies N, Alankus B, Weilemann A, Tzankov A, Brunner K, Ruff T, Kremer M, Keller UB, Lenz G, Ruland J. Lymphomagenic CARD11/BCL10/MALT1 signaling drives malignant B-cell proliferation via cooperative NF-κB and JNK activation. Proc Natl Acad Sci U S A. 112:E7230-8, 2015
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Kondyli V, Polykratis A, Ehlken H, Laura Ochoa-Callejero L, Straub BK, Krishna-Subramanian, SVan T-M, Curth H-M, Heise N, Weih F, Klein U, Schirmacher P, Kelliher M, Pasparakis M: NEMO prevents steatohepatitis and hepatocellular carcinoma by inhibiting RIPK1 kinase activity-mediated hepatocyte apoptosis. Cancer Cell 28:582-98, 2015
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Finkin S, Yuan D, Stein I, Taniguchi K, Weber A, Unger K, Browning JL, Goossens N, Nakagawa S, Gunasekaran G, Schwartz ME, Kobayashi M, Kumada H, Berger M, Pappo O, Rajewsky K, Hoshida Y, Karin M, Heikenwalder M, Ben-Neriah Y, Pikarsky E:  Ectopic lymphoid structures function as microniches for tumor progenitor cells in hepatocellular carcinoma. Nat Immunol.2015 Oct 26. doi: 10.1038/ni.3290. [Epub ahead of print]
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Nowicka AM, Häuselmann I, Borsig L, Bolduan S, Schindler M, Schraml P, Heikenwalder M, Moch H: A novel pVHL-independent but NEMO-driven pathway in renal cancer promotes HIF stabilization. Oncogene. 2015 Oct 26. doi: 10.1038/onc.2015.400. [Epub ahead of print]
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Savant S, La Porta S, Budnik A, Busch K, Hu J, Tisch N, Korn C, Valls AF, Benest AV, Terhardt D, Qu X, Adams RH, Baldwin HS, Ruiz de Almodóvar C, Rodewald HR, Augustin HG: The orphan receptor Tie1 controls angiogenesis and vascular remodeling by differentially regulating Tie2 in tip and stalk cells. Cell Rep. 12:1761-73, 2015
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DKFZ-ZMBH Alliance Forum
Tumor Microenvironment, Metabolism and Metastasis
September 28-30, 2015
Heidelberg, Germany
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Dietlein F, Kalb B, Jokic M, Noll EM, Strong A, Tharun L, Ozretić L, Künstlinger H, Kambartel K, Randerath WJ, Jüngst C, Schmitt A, Torgovnick A, Richters A, Rauh D, Siedek F, Persigehl T, Mauch C, Bartkova J, Bradley A, Sprick MR, Trumpp A, Rad R, Saur D, Bartek J, Wolf J, Büttner R, Thomas RK, Reinhardt HC: A Synergistic Interaction between Chk1- and MK2 Inhibitors in KRAS-Mutant Cancer. Cell. 162:146-59, 2015
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Poralla L, Stroh T, Erben U, Sittig M, Liebig S, Siegmund B, Glauben R: Histone deacetylase 5 regulates the inflammatory response of macrophages. J Cell Mol Med. doi: 10.1111/jcmm.12595, 2015 [Epub ahead of print]
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Zuckermann M, Hovestadt V, Knobbe-Thomsen CB, Zapatka M, Northcott PA, Schramm K, Belic J, Jones DT, Tschida B, Moriarity B, Largaespada D, Roussel MF, Korshunov A, Reifenberger G, Pfister SM, Lichter P, Kawauchi D, Gronych J: Somatic CRISPR/Cas9-mediated tumour suppressor disruption enables versatile brain tumour modelling. Nat Commun. 6:7391, 2015
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Peter Lichter receives the Johann-Georg-Zimmermann-Medaille for his lifetime achievment. He got awarded for his groundbreaking findings in the fields of molecular cytogenetic and the structure of genomes. Moreover, he developed novel technologies to decipher basic mechanisms in tumorigenesis.
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Busch K, Klapproth K, Barile M, Flossdorf M, Holland-Letz T, Schlenne SM, Reth M, Thomas Höfer T, Rodewald H-R: Fundamental properties of unperturbed haematopoiesis from stem cells in vivo. Nature, epub ahead of print, doi:10.1038, 2015
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Mogler C, Wieland M, König C, Hu J, Runge A, Korn C, Besemfelder E, Breitkopf-Heinlein K, Komljenovic D, Dooley S, Schirmacher P, Longerich T, Augustin HG: Hepatic stellate cell-expressed endosialin balances fibrogenesis and hepatocyte proliferation during liver damage. EMBO Mol Med. doi: 10.15252/emmm.201404246. [Epub ahead of print], 2015
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Rad R, Rad L, Wang W, Strong A, Ponstingl H, Bronner IF, Mayho M, Steiger K, Weber J, Hieber M, Veltkamp C, Eser S, Geumann U, Öllinger R, Zukowska M, Barenboim M, Maresch R, Cadiñanos J, Friedrich M, Varela I, Constantino-Casas F, Sarver A, Ten Hoeve J, Prosser H, Seidler B, Bauer J, Heikenwälder M, Metzakopian E, Krug A, Ehmer U, Schneider G, Knösel T, Rümmele P, Aust D, Grützmann R, Pilarsky C, Ning Z, Wessels L, Schmid RM, Quail MA, Vassiliou G, Esposito I, Liu P, Saur D, Bradley A: A conditional piggyBac transposition system for genetic screening in mice identifies oncogenic networks in pancreatic cancer. Nat Genet. 47:47-56, 2015
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Teodorczyk M, Kleber S, Wollny D, Sefrin JP, Aykut B, Mateos A, Herhaus P, Sancho-Martinez I, Hill O, Gieffers C, Sykora J, Weichert W, Eisen C, Trumpp A, Sprick MR, Bergmann F, Welsch T, Martin-Villalba A: CD95 promotes metastatic spread via Sck in pancreatic ductal adenocarcinoma. Cell Death Differ. doi: 10.1038/cdd.2014.217. [Epub ahead of print], 2015
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Northcott PA, Lee C, Zichner T, Stütz AM, Erkek S, Kawauchi D, Shih DJ, Hovestadt V, Zapatka M, Sturm D, Jones DT, Kool M, Remke M, Cavalli FM, Zuyderduyn S, Bader GD, VandenBerg S, Esparza LA, Ryzhova M, Wang W, Wittmann A, Stark S, Sieber L, Seker-Cin H, Linke L, Kratochwil F, Jäger N, Buchhalter I, Imbusch CD, Zipprich G, Raeder B, Schmidt S, Diessl N, Wolf S, Wiemann S, Brors B, Lawerenz C, Eils J, Warnatz HJ, Risch T, Yaspo ML, Weber UD, Bartholomae CC, von Kalle C, Turányi E, Hauser P, Sanden E, Darabi A, Siesjö P, Sterba J, Zitterbart K, Sumerauer D, van Sluis P, Versteeg R, Volckmann R, Koster J, Schuhmann MU, Ebinger M, Grimes HL, Robinson GW, Gajjar A, Mynarek M, von Hoff K, Rutkowski S, Pietsch T, Scheurlen W, Felsberg J, Reifenberger G, Kulozik AE, von Deimling A, Witt O, Eils R, Gilbertson RJ, Korshunov A, Taylor MD, Lichter P, Korbel JO, Wechsler-Reya RJ, Pfister SM: Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma. Nature 511:428-34, 2014
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Zhu Z, Khan MA, Weiler M, Blaes J, Jestaedt L, Geibert M, Zou P, Gronych J, Bernhardt O, Korshunov A, Bugner V, Lichter P, Radlwimmer B, Heiland S, Bendszus M, Wick W, Liu HK: Targeting self-renewal in high-grade brain tumors leads to loss of brain tumor stem cells and prolonged survival. Cell Stem Cell 15:185-98, 2014
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Dietlein F, Thelen L, Jokic M, Jachimowicz RD, Ivan L, Knittel G, Leeser U, van Oers J, Edelmann W, Heukamp LC, Reinhardt HC: A functional cancer genomics screen identifies a druggable synthetic lethal interaction between MSH3 and PRKDC. Cancer Discov. 4:592-605, 2014
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Huelsemann MF, Patz M, Beckmann L, Brinkmann K, Otto T, Fandrey J, Becker HJ, Theurich S, von Bergwelt-Baildon M, Pallasch CP, Zahedi RP, Kashkar H, Reinhardt HC, Hallek M, Wendtner CM, Frenzel LP: Hypoxia-induced p38 MAPK activation reduces Mcl-1 expression and facilitates sensitivity towards BH3 mimetics in chronic lymphocytic leukemia. Leukemia doi: 10.1038/leu.2014.320. [Epub ahead of print], 2014
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Roland Rad received the Dr. Emil Salzer Award for his research on the basic genetic mechsnisms underlying bowl cancer. Stefan Pfister, who focus on the genetic characteristics of brain tumors in children received the Walther and Christine Richtzenhain Award.
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Hellmut Augustin and Roland Eils received the Heidelberg Molecular Life Science (HMLS) Investigator Award for their effort towards promoting Heidelberg as a research center.
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Srivastava K, Hu J, Korn C, Savant S, Teichert M, Kapel SS, Jugold M, Besemfelder E, Thomas M, Pasparakis M, Augustin HG. Postsurgical adjuvant tumor therapy by combining anti-Angiopoietin-2 and metronomic chemotherapy limits metastatic growth. Cancer Cell 26:880-895, 2014.
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Gewies A, Gorka O, Bergmann H, Pechloff K, Petermann F, Jeltsch KM, Rudelius M, Kriegsmann M, Weichert W, Horsch M, Beckers J, Wurst W, Heikenwalder M, Korn T, Heissmeyer V, Ruland J. Uncoupling malt1 threshold function from paracaspase activity results in destructive autoimmune inflammation. Cell Rep. 9:1292-305, 2014.
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De Ponti A, Wiechert L, Stojanovic A, Longerich T, Marhenke S, Hogg N, Vogel A, Cerwenka A, Schirmacher P, Hess J, Angel P: Chronic liver inflammation and hepatocellular carcinogenesis are independent of S100A9. Int J Cancer. doi: 10.1002/ijc.29282. [Epub ahead of print], 2014
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Schönhuber N, Seidler B, Schuck K, Veltkamp C, Schachtler C, Zukowska M, Eser S, Feyerabend TB, Paul MC, Eser P, Klein S, Lowy AM, Banerjee R, Yang F, Lee CL, Moding EJ, Kirsch DG, Scheideler A, Alessi DR, Varela I, Bradley A, Kind A, Schnieke AE, Rodewald HR, Rad R, Schmid RM, Schneider G, Saur D. A next-generation dual-recombinase system for time- and host-specific targeting of pancreatic cancer .Nat Med. doi: 10.1038/nm.3646. [Epub ahead of print], 2014
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Jeltsch KM, Hu D, Brenner S, Zöller J, Heinz GA, Nagel D, Vogel KU, Rehage N, Warth SC, Edelmann SL, Gloury R, Martin N, Lohs C, Lech M, Stehklein JE, Geerlof A, Kremmer E, Weber A, Anders HJ, Schmitz I, Schmidt-Supprian M, Fu M, Holtmann H, Krappmann D, Ruland J, Kallies A, Heikenwalder M, Heissmeyer V. Cleavage of roquin and regnase-1 by the paracaspase MALT1 releases their cooperatively repressed targets to promote TH17 differentiation. Nat Immunol. 2014 Oct 5. doi: 10.1038/ni.3008. [Epub ahead of print]
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Wolf JM, Adili A, Piotrowitz K, Abdullah Z, Boege Y, Stemmer K, Ringelhan M, Simonavicius N, Egger M, Wohlleber D, Lorentzen A, Einer C, Schulz S, Clavel T, Protzer U, Thiele C, Zischka H, Moch H, Tschöpp M, Tumanov AV, Haller D, Unger K, Karin M, Kopf M, Knolle P, Weber A , Heikenwalder M: Metabolic Activation of Intrahepatic CD8+ T Cells and NKT-Cells Causes Nonalcoholic Steatohepatitis and Liver Cancer via Cross-Talk with Hepatocytes. Cancer Cell 26:549-64, 2014
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Kloster Seeon Meeting Report
Böck BC, Stein U, Schmitt CA, Augustin HG. Mouse models of human cancer. Cancer Res. 74:4671-5, 2014.
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Dannappel M, Vlantis K, Kumari S, Polykratis A, Kim C, Wachsmuth L, Eftychi C, Lin J, Corona T, Hermance N, Zelic M, Kirsch P, Basic M, Bleich A, Kelliher M, Pasparakis M. RIPK1 maintains epithelial homeostasis by inhibiting apoptosis and necroptosis. Nature. 513:90-4, 2014.
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Runge A, Hu J, Wieland M, Bergeest JP, Mogler C, Neumann A, Géraud C, Arnold B, Rohr K, Komljenovic D, Schirmacher P, Goerdt S, Augustin HG: An inducible hepatocellular carcinoma model for preclinical evaluation of anti-angiogenic therapy in adult mice. Cancer Res. 2014 [Epub ahead of print]
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Martins VC, Busch K, Juraeva D, Blum C, Ludwig C, Rasche V, Lasitschka F, Mastitsky SE, Brors B, Hielscher T, Fehling HJ, Rodewald HR: Cell competition is a tumour suppressor mechanism in the thymus. Nature 509:465-70, 2014
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Lucifora J, Xia Y, Reisinger F, Zhang K, Stadler D, Cheng X, Sprinzl MF, Koppensteiner H, Makowska Z, Volz T, Remouchamps C, Chou WM, Thasler WE, Hüser N, Durantel D, Liang TJ, Münk C, Heim MH, Browning JL, Dejardin E, Dandri M, Schindler M, Heikenwalder M, Protzer U: Specific and Nonhepatotoxic Degradation of Nuclear Hepatitis B Virus cccDNA. Science 343: 1221-8, 2014
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Glauben R, Sonnenberg E, Wetzel M, Mascagni P, Siegmund B. Histone deacetylase inhibitors modulate interleukin 6-dependent CD4+ T cell polarization in vitro and in vivo. J Biol Chem. 289: 6142-51, 2014
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Dörr JR, Yu Y, Milanovic M, Beuster G, Zasada C, Däbritz JH, Lisec J, Lenze D, Gerhardt A, Schleicher K, Kratzat S, Purfürst B, Walenta S, Mueller-Klieser W, Gräler M, Hummel M, Keller U, Buck AK, Dörken B, Willmitzer L, Reimann M, Kempa S, Lee S, Schmitt CA. Synthetic lethal metabolic targeting of cellular senescence in cancer therapy. Nature 501:421-5, 2013
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Press Release

1st International Kloster Seeon Meeting on Mouse Models of Human Cancers
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PCCCCircular No.1, January 2014: The Newsletter of the PCCC
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