TRR 209:  Leberkrebs - neue mechanistische und therapeutische Konzepte in einem soliden Tumormodell

• Fachliche Zuordnung: Medizin
• Förderung: Förderung von 2017 bis 2022
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 314905040

• Erstellungsjahr: 2024

Zusammenfassung der Projektergebnisse

Leberkrebs ist die sechsthäufigste maligne Tumorerkrankung und die dritthäufigste krebsbedingte Todesursache. Er setzt sich zusammen aus hepatozellulärem Karzinom, intrahepatischem Cholangiokarzinom und Leberkarzinomen gemischter Differenzierung. Leberkrebs stellt eine Tumorerkrankung mit herausragendem Modellcharakter dar; seine Ursachen sind bekannt, im Einzelnen chronische Virusinfektionen (Hepatitis B/C), metabolische Erkrankungen (v.a. Nichtalkoholische Steatohepatitis), chronische Toxinbelastung (Alkohol, Aflatoxin) und chronische Entzündung der Leber (Hepatitis). Dennoch ist noch zu wenig verstanden, wie onkogene Mechanismen die Tumorentstehung verursachen, wie letale Tumorprogression in Interaktion mit dem Tumormikromilieu erfolgt und wie man neue mechanistische Erkenntnisse in bessere Therapieansätze umsetzen kann. Exzellente Modellsysteme, insbesondere innovative Mausmodelle, und bestens annotierte Leberkrebskohorten waren beste Voraussetzungen, um diese Kernfragen erfolgreich anzugehen. Der SFB/TR 209 hatte das Ziel, neue mechanistische Erkenntnisse und Interventionsstrategien zu etablieren, die über den Leberkrebs hinaus auch für andere solide Tumorerkrankungen bedeutsam sind, und diese über die enge Anbindung an etablierte klinische, translationale Strukturen erfolgreich umzusetzen. Um diese Ziele zu erreichen, führte der SFB/TR die Expertise international führender Leberkrebs-Forscher und neueste Modellsysteme zusammen, um zentrale mechanistische und interventionelle Fragen gezielt und koordiniert anzugehen. Er war der weltweit größte Forschungsverbund, der sich mit Leberkrebs beschäftigte und der bereits nach der ersten Förderphase durch seine Forschungsdaten, translationalen Bemühungen, Konferenzen und Workshops eine national und international führende Bedeutung erlangte. Der SFB/TR war an den drei Partnerstandorten eng mit etablierten und starken, klinischen und translationalen Strukturen zum Leberkrebs verbunden. Während der gesamten ersten Förderperiode wurden durchgängig Maßnahmen zur wissenschaftlichen Nachwuchsförderung, Vereinbarkeit von Familie und Beruf und Gleichstellung integriert und in vollem Umfang durchgeführt. Wegweisende Erkenntnisse in der ersten Förderperiode waren die Identifizierung neuartiger Leberkrebs-initiierender Mechanismen, die Entschlüsselung von Leberkrebs-fördernden Mechanismen und die Identifizierung neuartiger therapeutischer Prinzipien, die beim Leberkrebs angegangen werden können.

Projektbezogene Publikationen (Auswahl)

• Anti-tumor medicament based on adenovirus”, EP3274363
  Lauer; Eggert & Kühnel
  
• EP000003475425A1: Treatments of non-alcoholic steatohepatitis (NASH)
  Zender
  
• Europ. patent 3274363 (granted) – Anti-tumor medicament based on adenovirus
  Kühnel
  
• P000002729146B1: Medicament for treatment of liver cancer
  Zender
  
• Therapie von Infektionen und Tumoren mit Hilfe einer Prime-Boost Vakzine aus Liposomen und einer costimulation-assistierten T-Zell Vakzinierung (COAT) 15-00358/ M1073PCT-EP
  Wirth
  
• WO002006007520A1: Medicament for liver regeneration and treatment of liver failure
  Zender
  
• WO2008/104387 “Use of inhibitors of the degradation of p27, in particular Argyrin and derivatives thereof, for the treatment of proliferative diseases”
  Malek
  
• WO2010/006682 “Method for producing intermediates for the production of novel macrocycles that are inhibitors of the proteasomic degradation of p27, such as argyrin and derivatives thereof, and uses of said macrocycles”
  Malek
  
• WO2011/073173 “Improved method for producing intermediates for the production of macrocycles that are inhibitors of the proteasomic degradation of p27, such as argyrin and derivatives thereof”
  Malek
  
• WO2013/007708 A1, Medicament for the treatment of liver cancer
  Zender; Rudalska & Dauch
  
• A Dual Role of Caspase-8 in Triggering and Sensing Proliferation-Associated DNA Damage, a Key Determinant of Liver Cancer Development. Cancer Cell, 32(3), 342-359.e10.
  Boege, Yannick; Malehmir, Mohsen; Healy, Marc E.; Bettermann, Kira; Lorentzen, Anna; Vucur, Mihael; Ahuja, Akshay K.; Böhm, Friederike; Mertens, Joachim C.; Shimizu, Yutaka; Frick, Lukas; Remouchamps, Caroline; Mutreja, Karun; Kähne, Thilo; Sundaravinayagam, Devakumar; Wolf, Monika J.; Rehrauer, Hubert; Koppe, Christiane; Speicher, Tobias ... & Weber, Achim
  
• Cellular senescence in gastrointestinal diseases: from pathogenesis to therapeutics. Nature Reviews Gastroenterology & Hepatology, 15(2), 81-95.
  Frey, Nina; Venturelli, Sascha; Zender, Lars & Bitzer, Michael
  
• Immune-mediated effects targeting hepatitis C virus in a syngeneic replicon cell transplantation mouse model. Gut, 67(8), 1525-1535.
  Levander, Sepideh; Holmström, Fredrik; Frelin, Lars; Ahlén, Gustaf; Rupp, Daniel; Long, Gang; Bartenschlager, Ralf & Sällberg, Matti
  
• Induction of Chromosome Instability by Activation of Yes-Associated Protein and Forkhead Box M1 in Liver Cancer. Gastroenterology, 152(8), 2037-2051.e22.
  Weiler, Sofia M.E.; Pinna, Federico; Wolf, Thomas; Lutz, Teresa; Geldiyev, Aman; Sticht, Carsten; Knaub, Maria; Thomann, Stefan; Bissinger, Michaela; Wan, Shan; Rössler, Stephanie; Becker, Diana; Gretz, Norbert; Lang, Hauke; Bergmann, Frank; Ustiyan, Vladimir; Kalin, Tatiana V.; Singer, Stephan; Lee, Ju-Seog ... & Breuhahn, Kai
  
• Kupffer Cell-Derived Tnf Triggers Cholangiocellular Tumorigenesis through JNK due to Chronic Mitochondrial Dysfunction and ROS. Cancer Cell, 31(6), 771-789.e6.
  Yuan, Detian; Huang, Shan; Berger, Emanuel; Liu, Lei; Gross, Nina; Heinzmann, Florian; Ringelhan, Marc; Connor, Tracy O.; Stadler, Mira; Meister, Michael; Weber, Julia; Öllinger, Rupert; Simonavicius, Nicole; Reisinger, Florian; Hartmann, Daniel; Meyer, Rüdiger; Reich, Maria; Seehawer, Marco; Leone, Valentina ... & Heikenwalder, Mathias
  
• Oncolytic measles virus, EP2605783 (granted 25.3.2015); US9272008 B2 (granted 1.3.2016); US9795643 (granted 24.10.2017); JP6001535 (granted 9.9.2016); MX/a/2013/001930
  Lauer; Eggert & Kühnel
  
• Multiplexed orthogonal genome editing and transcriptional activation by Cas12a. Nature Methods, 16(1), 51-54.
  Breinig, Marco; Schweitzer, Anabel Y.; Herianto, Anna M.; Revia, Steffie; Schaefer, Lisa; Wendler, Lena; Cobos, Galvez Ana & Tschaharganeh, Darjus F.
  
• Necroptosis microenvironment directs lineage commitment in liver cancer. Nature, 562(7725), 69-75.
  Seehawer, Marco; Heinzmann, Florian; D.’Artista, Luana; Harbig, Jule; Roux, Pierre-François; Hoenicke, Lisa; Dang, Hien; Klotz, Sabrina; Robinson, Lucas; Doré, Grégory; Rozenblum, Nir; Kang, Tae-Won; Chawla, Rishabh; Buch, Thorsten; Vucur, Mihael; Roth, Mareike; Zuber, Johannes; Luedde, Tom; Sipos, Bence ... & Zender, Lars
  
• Optimized base editors enable efficient editing in cells, organoids and mice. Nature Biotechnology, 36(9), 888-893.
  Zafra, Maria Paz; Schatoff, Emma M.; Katti, Alyna; Foronda, Miguel; Breinig, Marco; Schweitzer, Anabel Y.; Simon, Amber; Han, Teng; Goswami, Sukanya; Montgomery, Emma; Thibado, Jordana; Kastenhuber, Edward R.; Sánchez-Rivera, Francisco J.; Shi, Junwei; Vakoc, Christopher R.; Lowe, Scott W.; Tschaharganeh, Darjus F. & Dow, Lukas E.
  
• Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a non-randomised, open-label phase 2 trial. The Lancet Oncology, 19(7), 940-952.
  Zhu, Andrew X.; Finn, Richard S.; Edeline, Julien; Cattan, Stephane; Ogasawara, Sadahisa; Palmer, Daniel; Verslype, Chris; Zagonel, Vittorina; Fartoux, Laetitia; Vogel, Arndt; Sarker, Debashis; Verset, Gontran; Chan, Stephen L.; Knox, Jennifer; Daniele, Bruno; Webber, Andrea L.; Ebbinghaus, Scot W.; Ma, Junshui; Siegel, Abby B. ... & Yamashita, Tatsuya
  
• PTBP1-Mediated Alternative Splicing Regulates the Inflammatory Secretome and the Pro-tumorigenic Effects of Senescent Cells. Cancer Cell, 34(1), 85-102.e9.
  Georgilis, Athena; Klotz, Sabrina; Hanley, Christopher J.; Herranz, Nicolas; Weirich, Benedikt; Morancho, Beatriz; Leote, Ana Carolina; D.'Artista, Luana; Gallage, Suchira; Seehawer, Marco; Carroll, Thomas; Dharmalingam, Gopuraja; Wee, Keng Boon; Mellone, Marco; Pombo, Joaquim; Heide, Danijela; Guccione, Ernesto; Arribas, Joaquín; Barbosa-Morais, Nuno L. ... & Gil, Jesús
  
• The immunology of hepatocellular carcinoma. Nature Immunology, 19(3), 222-232.
  Ringelhan, Marc; Pfister, Dominik; O.’Connor, Tracy; Pikarsky, Eli & Heikenwalder, Mathias
  
• WO002018153966A1: Radiolabeled beta-galactosidase substrate for PET imaging of Senescence
  Zender
  
• From NASH to HCC: current concepts and future challenges. Nature Reviews Gastroenterology & Hepatology, 16(7), 411-428.
  Anstee, Quentin M.; Reeves, Helen L.; Kotsiliti, Elena; Govaere, Olivier & Heikenwalder, Mathias
  
• Genetically modified paramyxovirus for the treatment of tumor diseases, DE 102010018961 (granted 20.9.2012); US9821016 (granted 21.11.2017); CHINA ZL2011800292786 (granted 27.4.2018); EP 2 560 986 B1 (granted 02.06.2021); INDIA 323745
  Bitzer; Armeanu-Ebinger; Bossow; Lauer; Neubert & Zimmermann
  
• GPD1 Specifically Marks Dormant Glioma Stem Cells with a Distinct Metabolic Profile. Cell Stem Cell, 25(2), 241-257.e8.
  Rusu, Patricia; Shao, Chunxuan; Neuerburg, Anna; Acikgöz, Azer Aylin; Wu, Yonghe; Zou, Peng; Phapale, Prasad; Shankar, Tchirupura S.; Döring, Kristina; Dettling, Steffen; Körkel-Qu, Huiqin; Bekki, Gözde; Costa, Barbara; Guo, Te; Friesen, Olga; Schlotter, Magdalena; Heikenwalder, Mathias; Tschaharganeh, Darjus F.; Bukau, Bernd ... & Liu, Hai-Kun
  
• Indelibly Stamped by Hepatitis C Virus Infection: Persistent Epigenetic Signatures Increasing Liver Cancer Risk. Gastroenterology, 156(8), 2130-2133.
  Lohmann, Volker & Bartenschlager, Ralf
  
• Nuclear Translocation of RELB Is Increased in Diseased Human Liver and Promotes Ductular Reaction and Biliary Fibrosis in Mice. Gastroenterology, 156(4), 1190-1205.e14.
  Elßner, Christin; Goeppert, Benjamin; Longerich, Thomas; Scherr, Anna-Lena; Stindt, Jan; Nanduri, Lahiri Kanth; Rupp, Christian; Kather, Jakob Nikolas; Schmitt, Nathalie; Kautz, Nicole; Breuhahn, Kai; Ismail, Lars; Heide, Danijela; Hetzer, Jenny; García-Beccaria, María; Hövelmeyer, Nadine; Waisman, Ari; Urbanik, Toni; Mueller, Sebastian ... & Köhler, Bruno Christian
  
• p53 Represses the Mevalonate Pathway to Mediate Tumor Suppression. Cell, 176(3), 564-580.e19.
  Moon, Sung-Hwan; Huang, Chun-Hao; Houlihan, Shauna L.; Regunath, Kausik; Freed-Pastor, William A.; Morris, John P.; Tschaharganeh, Darjus F.; Kastenhuber, Edward R.; Barsotti, Anthony M.; Culp-Hill, Rachel; Xue, Wen; Ho, Yu-Jui; Baslan, Timour; Li, Xiang; Mayle, Allison; de Stanchina, Elisa; Zender, Lars; Tong, David R.; D.’Alessandro, Angelo ... & Prives, Carol
  
• Peritumoral activation of the Hippo pathway effectors YAP and TAZ suppresses liver cancer in mice. Science, 366(6468), 1029-1034.
  Moya, Iván M.; Castaldo, Stéphanie A.; Van den Mooter, Laura; Soheily, Soheil; Sansores-Garcia, Leticia; Jacobs, Jelle; Mannaerts, Inge; Xie, Jun; Verboven, Elisabeth; Hillen, Hanne; Algueró-Nadal, Ana; Karaman, Ruchan; Van Haele, Matthias; Kowalczyk, Weronika; De Waegeneer, Maxime; Verhulst, Stefaan; Karras, Panagiotis; van Huffel, Leen; Zender, Lars ... & Halder, Georg
  
• Platelet GPIbα is a mediator and potential interventional target for NASH and subsequent liver cancer. Nature Medicine, 25(4), 641-655.
  Malehmir, Mohsen; Pfister, Dominik; Gallage, Suchira; Szydlowska, Marta; Inverso, Donato; Kotsiliti, Elena; Leone, Valentina; Peiseler, Moritz; Surewaard, Bas G. J.; Rath, Dominik; Ali, Adnan; Wolf, Monika Julia; Drescher, Hannah; Healy, Marc E.; Dauch, Daniel; Kroy, Daniela; Krenkel, Oliver; Kohlhepp, Marlene; Engleitner, Thomas ... & Heikenwalder, Mathias
  
• RSPO2 gene rearrangement: a powerful driver of β-catenin activation in liver tumours. Gut, 68(7), 1287-1296.
  Longerich, Thomas; Endris, Volker; Neumann, Olaf; Rempel, Eugen; Kirchner, Martina; Abadi, Zahra; Uhrig, Sebastian; Kriegsmann, Mark; Weiss, Karl Heinz; Breuhahn, Kai; Mehrabi, Arianeb; Weber, Tim Frederik; Wilkens, Ludwig; Straub, Beate K.; Rosenwald, Andreas; Schulze, Falko; Brors, Benedikt; Froehling, Stefan; Pellegrino, Rossella ... & Stenzinger, Albrecht
  
• A dual role for hepatocyte-intrinsic canonical NF-κB signalinginvirus control. Journal of Hepatology, 72(5), 960-975.
  Namineni, Sukumar; O.'Connor, Tracy; Faure-Dupuy, Suzanne; Johansen, Pål; Riedl, Tobias; Liu, Kaijing; Xu, Haifeng; Singh, Indrabahadur; Shinde, Prashant; Li, Fanghui; Pandyra, Aleksandra; Sharma, Piyush; Ringelhan, Marc; Muschaweckh, Andreas; Borst, Katharina; Blank, Patrick; Lampl, Sandra; Neuhaus, Katharina; Durantel, David ... & Heikenwalder, Mathias
  
• Genomic Characterization of Cholangiocarcinoma in Primary Sclerosing Cholangitis Reveals Therapeutic Opportunities. Hepatology, 72(4), 1253-1266.
  Goeppert, Benjamin; Folseraas, Trine; Roessler, Stephanie; Kloor, Matthias; Volckmar, Anna‐Lena; Endris, Volker; Buchhalter, Ivo; Stenzinger, Albrecht; Grzyb, Krzysztof; Grimsrud, Marit M.; Gornicka, Barbara; von Seth, Erik; Reynolds, Gary M.; Franke, Andre; Gotthardt, Daniel N.; Mehrabi, Arianeb; Cheung, Angela; Verheij, Joanne; Arola, Johanna ... & Karlsen, Tom H.
  
• Gut Microbiome Directs Hepatocytes to Recruit MDSCs and Promote Cholangiocarcinoma. Cancer Discovery, 11(5), 1248-1267.
  Zhang, Qianfei; Ma, Chi; Duan, Yi; Heinrich, Bernd; Rosato, Umberto; Diggs, Laurence P.; Ma, Lichun; Roy, Soumen; Fu, Qiong; Brown, Zachary J.; Wabitsch, Simon; Thovarai, Vishal; Fu, Jianyang; Feng, Dechun; Ruf, Benjamin; Cui, Linda L.; Subramanyam, Varun; Frank, Karen M.; Wang, Sophie ... & Greten, Tim F.
  
• The nf-core framework for community-curated bioinformatics pipelines. Nature Biotechnology, 38(3), 276-278.
  Ewels, Philip A.; Peltzer, Alexander; Fillinger, Sven; Patel, Harshil; Alneberg, Johannes; Wilm, Andreas; Garcia, Maxime Ulysse; Di Tommaso, Paolo & Nahnsen, Sven
  
• Author Correction: Auto-aggressive CXCR6+ CD8 T cells cause liver immune pathology in NASH. Nature, 593(7860), E14-E14.
  Dudek, Michael; Pfister, Dominik; Donakonda, Sainitin; Filpe, Pamela; Schneider, Annika; Laschinger, Melanie; Hartmann, Daniel; Hüser, Norbert; Meiser, Philippa; Bayerl, Felix; Inverso, Donato; Wigger, Jennifer; Sebode, Marcial; Öllinger, Rupert; Rad, Roland; Hegenbarth, Silke; Anton, Martina; Guillot, Adrien; Bowman, Andrew ... & Knolle, Percy A.
  
• CD40-mediated immune cell activation enhances response to anti-PD-1 in murine intrahepatic cholangiocarcinoma. Journal of Hepatology, 74(5), 1145-1154.
  Diggs, Laurence P.; Ruf, Benjamin; Ma, Chi; Heinrich, Bernd; Cui, Linda; Zhang, Qianfei; McVey, John C.; Wabitsch, Simon; Heinrich, Sophia; Rosato, Umberto; Lai, Walter; Subramanyam, Varun; Longerich, Thomas; Loosen, Sven H.; Luedde, Tom; Neumann, Ulf Peter; Desar, Sabina; Kleiner, David; Gores, Gregory ... & Greten, Tim F.
  
• Hepatocyte-specific NRF2 activation controls fibrogenesis and carcinogenesis in steatohepatitis. Journal of Hepatology, 74(3), 638–648.
  Mohs, Antje; Otto, Tobias; Schneider, Kai Markus; Peltzer, Mona; Boekschoten, Mark; Holland, Christian H.; Hudert, Christian A.; Kalveram, Laura; Wiegand, Susanna; Saez-Rodriguez, Julio; Longerich, Thomas; Hengstler, Jan G. & Trautwein, Christian
  
• Histone H3K27 demethylase KDM6A is an epigenetic gatekeeper of mTORC1 signalling in cancer. Gut, 71(8), 1613-1628.
  Revia, Steffie; Seretny, Agnieszka; Wendler, Lena; Banito, Ana; Eckert, Christoph; Breuer, Kersten; Mayakonda, Anand; Lutsik, Pavlo; Evert, Matthias; Ribback, Silvia; Gallage, Suchira; Chikh, Bakri Ismaiel; Breuhahn, Kai; Schirmacher, Peter; Heinrich, Stefan; Gaida, Matthias M.; Heikenwälder, Mathias; Calvisi, Diego F.; Plass, Christoph ... & Tschaharganeh, Darjus F.
  
• Immunotherapies for hepatocellular carcinoma. Nature Reviews Clinical Oncology, 19(3), 151-172.
  Llovet, Josep M.; Castet, Florian; Heikenwalder, Mathias; Maini, Mala K.; Mazzaferro, Vincenzo; Pinato, David J.; Pikarsky, Eli; Zhu, Andrew X. & Finn, Richard S.
  
• Integrative analysis reveals early and distinct genetic and epigenetic changes in intraductal papillary and tubulopapillary cholangiocarcinogenesis. Gut, 71(2), 391-401.
  Goeppert, Benjamin; Stichel, Damian; Toth, Reka; Fritzsche, Sarah; Loeffler, Moritz Anton; Schlitter, Anna Melissa; Neumann, Olaf; Assenov, Yassen; Vogel, Monika Nadja; Mehrabi, Arianeb; Hoffmann, Katrin; Köhler, Bruno; Springfeld, Christoph; Weichenhan, Dieter; Plass, Christoph; Esposito, Irene; Schirmacher, Peter; von Deimling, Andreas & Roessler, Stephanie
  
• Integrative genomics highlights opportunities for innovative therapies targeting the tumor microenvironment in gallbladder cancer. Journal of Hepatology, 74(5), 1018-1020.
  Roessler, Stephanie; Edeline, Julien; Schirmacher, Peter & Coulouarn, Cédric
  
• LXRα activation and Raf inhibition trigger lethal lipotoxicity in liver cancer. Nature Cancer, 2(2), 201-217.
  Rudalska, Ramona; Harbig, Jule; Snaebjornsson, Marteinn T.; Klotz, Sabrina; Zwirner, Stefan; Taranets, Liudmyla; Heinzmann, Florian; Kronenberger, Thales; Forster, Michael; Cui, Wei; D.’Artista, Luana; Einig, Elias; Hinterleitner, Martina; Schmitz, Werner; Dylawerska, Agata; Kang, Tae-Won; Poso, Antti; Rosenfeldt, Mathias T.; Malek, Nisar P. ... & Dauch, Daniel
  
• Molecular characterisation of hepatocellular carcinoma in patients with non-alcoholic steatohepatitis. Journal of Hepatology, 75(4), 865-878.
  Pinyol, Roser; Torrecilla, Sara; Wang, Huan; Montironi, Carla; Piqué-Gili, Marta; Torres-Martin, Miguel; Wei-Qiang, Leow; Willoughby, Catherine E.; Ramadori, Pierluigi; Andreu-Oller, Carmen; Taik, Patricia; Lee, Youngmin A.; Moeini, Agrin; Peix, Judit; Faure-Dupuy, Suzanne; Riedl, Tobias; Schuehle, Svenja; Oliveira, Claudia P.; Alves, Venancio A. ... & Llovet, Josep M.
  
• NASH limits anti-tumour surveillance in immunotherapy-treated HCC. Nature, 592(7854), 450-456.
  Pfister, Dominik; Núñez, Nicolás Gonzalo; Pinyol, Roser; Govaere, Olivier; Pinter, Matthias; Szydlowska, Marta; Gupta, Revant; Qiu, Mengjie; Deczkowska, Aleksandra; Weiner, Assaf; Müller, Florian; Sinha, Ankit; Friebel, Ekaterina; Engleitner, Thomas; Lenggenhager, Daniela; Moncsek, Anja; Heide, Danijela; Stirm, Kristin; Kosla, Jan ... & Heikenwalder, Mathias
  
• SpaceM reveals metabolic states of single cells. Nature Methods, 18(7), 799-805.
  Rappez, Luca; Stadler, Mira; Triana, Sergio; Gathungu, Rose Muthoni; Ovchinnikova, Katja; Phapale, Prasad; Heikenwalder, Mathias & Alexandrov, Theodore
  
• The Co‐mutational Spectrum Determines the Therapeutic Response in Murine FGFR2 Fusion‐Driven Cholangiocarcinoma. Hepatology, 74(3), 1357-1370.
  Kendre, Gajanan; Marhenke, Silke; Lorz, Georgina; Becker, Diana; Reineke‐Plaaß, Tanja; Poth, Tanja; Murugesan, Karthikeyan; Kühnel, Florian; Woller, Norman; Wirtz, Ralph M.; Pich, Andreas; Marquardt, Jens U.; Saborowski, Michael; Vogel, Arndt & Saborowski, Anna
  
• The immunological and metabolic landscape in primary and metastatic liver cancer. Nature Reviews Cancer, 21(9), 541-557.
  Li, Xin; Ramadori, Pierluigi; Pfister, Dominik; Seehawer, Marco; Zender, Lars & Heikenwalder, Mathias
  
• Timed Ang2-Targeted Therapy Identifies the Angiopoietin–Tie Pathway as Key Regulator of Fatal Lymphogenous Metastasis. Cancer Discovery, 11(2), 424-445.
  Gengenbacher, Nicolas; Singhal, Mahak; Mogler, Carolin; Hai, Ling; Milde, Laura; Pari, Ashik Ahmed Abdul; Besemfelder, Eva; Fricke, Claudine; Baumann, Daniel; Gehrs, Stephanie; Utikal, Jochen; Felcht, Moritz; Hu, Junhao; Schlesner, Matthias; Offringa, Rienk; Chintharlapalli, Sudhakar R. & Augustin, Hellmut G.
  
• Transcriptome Profiling Identifies TIGIT as a Marker of T‐Cell Exhaustion in Liver Cancer. Hepatology, 73(4), 1399-1418.
  Ostroumov, Dmitrij; Duong, Steven; Wingerath, Jessica; Woller, Norman; Manns, Michael P.; Timrott, Kai; Kleine, Moritz; Ramackers, Wolf; Roessler, Stephanie; Nahnsen, Sven; Czemmel, Stefan; Dittrich‐Breiholz, Oliver; Eggert, Tobias; Kühnel, Florian & Wirth, Thomas C.
  
• XCR1+ type 1 conventional dendritic cells drive liver pathology in non-alcoholic steatohepatitis. Nature Medicine, 27(6), 1043-1054.
  Deczkowska, Aleksandra; David, Eyal; Ramadori, Pierluigi; Pfister, Dominik; Safran, Michal; Li, Baoguo; Giladi, Amir; Jaitin, Diego Adhemar; Barboy, Oren; Cohen, Merav; Yofe, Ido; Gur, Chamutal; Shlomi-Loubaton, Shir; Henri, Sandrine; Suhail, Yousuf; Qiu, Mengjie; Kam, Shing; Hermon, Hila; Lahat, Eylon ... & Amit, Ido
  
• A researcher’s guide to preclinical mouse NASH models. Nature Metabolism, 4(12), 1632-1649.
  Gallage, Suchira; Avila, Jose Efren Barragan; Ramadori, Pierluigi; Focaccia, Enrico; Rahbari, Mohammad; Ali, Adnan; Malek, Nisar P.; Anstee, Quentin M. & Heikenwalder, Mathias
  
• Combined hepatocellular-cholangiocarcinoma derives from liver progenitor cells and depends on senescence and IL-6 trans-signaling. Journal of Hepatology, 77(6), 1631-1641.
  Rosenberg, Nofar; Van Haele, Matthias; Lanton, Tali; Brashi, Neta; Bromberg, Zohar; Adler, Hanan; Giladi, Hilla; Peled, Amnon; Goldenberg, Daniel S.; Axelrod, Jonathan H.; Simerzin, Alina; Chai, Chofit; Paldor, Mor; Markezana, Auerlia; Yaish, Dayana; Shemulian, Zohar; Gross, Dvora; Barnoy, Shanny; Gefen, Maytal ... & Galun, Eithan
  
• Hepatocellular carcinoma. The Lancet, 400(10360), 1345-1362.
  Vogel, Arndt; Meyer, Tim; Sapisochin, Gonzalo; Salem, Riad & Saborowski, Anna
  
• Medical therapy of HCC. Journal of Hepatology, 76(1), 208-210.
  Vogel, Arndt & Saborowski, Anna
  
• New kid on the block: Netrin‐1 as a novel player in the delicate molecular network of hepatic inflammation. Hepatology, 76(5), 1237-1239.
  Goeppert, Benjamin & Roessler, Stephanie
  
• Charting co-mutation patterns associated with actionable drivers in intrahepatic cholangiocarcinoma. Journal of Hepatology, 78(3), 614-626.
  Kendre, Gajanan; Murugesan, Karthikeyan; Brummer, Tilman; Segatto, Oreste; Saborowski, Anna & Vogel, Arndt
  
• Molecular Markers of Response to Anti-PD1 Therapy in Advanced Hepatocellular Carcinoma. Gastroenterology, 164(1), 72-88.e18.
  Haber, Philipp K.; Castet, Florian; Torres-Martin, Miguel; Andreu-Oller, Carmen; Puigvehí, Marc; Miho, Maeda; Radu, Pompilia; Dufour, Jean-Francois; Verslype, Chris; Zimpel, Carolin; Marquardt, Jens U.; Galle, Peter R.; Vogel, Arndt; Bathon, Melanie; Meyer, Tim; Labgaa, Ismail; Digklia, Antonia; Roberts, Lewis R.; Mohamed, Ali Mohamed A. ... & Llovet, Josep M.
  
• MYC determines lineage commitment in KRAS-driven primary liver cancer development. Journal of Hepatology, 79(1), 141-149.
  D.’Artista, Luana; Moschopoulou, Athina Anastasia; Barozzi, Iros; Craig, Amanda J.; Seehawer, Marco; Herrmann, Lea; Minnich, Martina; Kang, Tae-Won; Rist, Elke; Henning, Melanie; Klotz, Sabrina; Heinzmann, Florian; Harbig, Jule; Sipos, Bence; Longerich, Thomas; Eilers, Martin; Dauch, Daniel; Zuber, Johannes; Wang, Xin Wei & Zender, Lars