Bcl-x


Journal

Liver international : official journal of the International Association for the Study of the Liver
ISSN: 1478-3231
Titre abrégé: Liver Int
Pays: United States
ID NLM: 101160857

Informations de publication

Date de publication:
12 2022
Historique:
revised: 26 07 2022
received: 11 01 2022
accepted: 08 08 2022
pubmed: 20 8 2022
medline: 25 11 2022
entrez: 19 8 2022
Statut: ppublish

Résumé

Intrahepatic, perihilar, and distal cholangiocarcinoma (iCCA, pCCA, dCCA) are highly malignant tumours with increasing mortality rates due to therapy resistances. Among the mechanisms mediating resistance, overexpression of anti-apoptotic Bcl-2 proteins (Bcl-2, Bcl-x

Identifiants

pubmed: 35983950
doi: 10.1111/liv.15392
doi:

Substances chimiques

bcl-X Protein 0
Myeloid Cell Leukemia Sequence 1 Protein 0
Proto-Oncogene Proteins c-bcl-2 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2855-2870

Informations de copyright

© 2022 The Authors. Liver International published by John Wiley & Sons Ltd.

Références

Florio AA, Ferlay J, Znaor A, et al. Global trends in intrahepatic and extrahepatic cholangiocarcinoma incidence from 1993 to 2012. Cancer. 2020;126(11):2666-2678. doi:10.1002/cncr.32803
Banales JM, Marin JJG, Lamarca A, et al. Cholangiocarcinoma 2020: the next horizon in mechanisms and management. Nat Rev Gastroenterol Hepatol. 2020;17:557-588. doi:10.1038/s41575-020-0310-z
Bertuccio P, Malvezzi M, Carioli G, et al. Global trends in mortality from intrahepatic and extrahepatic cholangiocarcinoma. J Hepatol. 2019;71:104-114. doi:10.1016/j.jhep.2019.03.013
Khan SA, Davidson BR, Goldin RD, et al. Guidelines for the diagnosis and treatment of cholangiocarcinoma: an update. Gut. 2012;61:1657-1669. doi:10.1136/gutjnl-2011-301748
Rizvi S, Khan SA, Hallemeier CL, Kelley RK, Gores GJ. Cholangiocarcinoma - evolving concepts and therapeutic strategies. Nat Rev Clin Oncol. 2018;15:95-111. doi:10.1038/nrclinonc.2017.157
Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100:57-70. doi:10.1016/s0092-8674(00)81683-9
Cory S, Adams JM. The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer. 2002;2:647-656. doi:10.1038/nrc883
Scherr AL, Gdynia G, Salou M, et al. Bcl-xL is an oncogenic driver in colorectal cancer. Cell Death Dis. 2016;7:e2342. doi:10.1038/cddis.2016.233
Lee EF, Harris TJ, Tran S, et al. BCL-XL and MCL-1 are the key BCL-2 family proteins in melanoma cell survival. Cell Death Dis. 2019;10:342. doi:10.1038/s41419-019-1568-3
Czabotar PE, Lessene G, Strasser A, Adams JM. Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy. Nat Rev Mol Cell Biol. 2014;15:49-63. doi:10.1038/nrm3722
Ashkenazi A, Fairbrother WJ, Leverson JD, Souers AJ. From basic apoptosis discoveries to advanced selective BCL-2 family inhibitors. Nat Rev Drug Discov. 2017;16:273-284. doi:10.1038/nrd.2016.253
Roberts AW, Huang D. Targeting BCL2 with BH3 mimetics: basic science and clinical application of Venetoclax in chronic lymphocytic leukemia and related B cell malignancies. Clin Pharmacol Ther. 2017;101:89-98. doi:10.1002/cpt.553
DiNardo CD, Jonas BA, Pullarkat V, et al. Azacitidine and Venetoclax in previously untreated acute myeloid leukemia. N Engl J Med. 2020;383:617-629. doi:10.1056/NEJMoa2012971
Fischer K, al-Sawaf O, Bahlo J, et al. Venetoclax and Obinutuzumab in patients with CLL and coexisting conditions. N Engl J Med. 2019;380:2225-2236. doi:10.1056/NEJMoa1815281
Leverson JD, Phillips DC, Mitten MJ, et al. Exploiting selective BCL-2 family inhibitors to dissect cell survival dependencies and define improved strategies for cancer therapy. Sci Transl Med. 2015;7:279-240. doi:10.1126/scitranslmed.aaa4642
Inoue-Yamauchi A, Jeng PS, Kim K, et al. Targeting the differential addiction to anti-apoptotic BCL-2 family for cancer therapy. Nat Commun. 2017;8:16078. doi:10.1038/ncomms16078
Scherr AL, Mock A, Gdynia G, et al. Identification of BCL-XL as highly active survival factor and promising therapeutic target in colorectal cancer. Cell Death Dis. 2020;11:875. doi:10.1038/s41419-020-03092-7
Horak P, Heining C, Kreutzfeldt S, et al. Comprehensive genomic and transcriptomic analysis for guiding therapeutic decisions in patients with rare cancers. Cancer Discov. 2021;11:2780-2795. doi:10.1158/2159-8290.CD-21-0126
Horak P, Klink B, Heining C, et al. Precision oncology based on omics data: the NCT Heidelberg experience. Int J Cancer. 2017;141:877-886. doi:10.1002/ijc.30828
Ding H, Douglass EF Jr, Sonabend AM, et al. Quantitative assessment of protein activity in orphan tissues and single cells using the metaVIPER algorithm. Nat Commun. 2018;9:1471. doi:10.1038/s41467-018-03843-3
Elssner C, Goeppert B, Longerich T, et al. Nuclear translocation of RELB is increased in diseased human liver and promotes ductular reaction and biliary fibrosis in mice. Gastroenterology. 2019;156:1190-1205 e1114. doi:10.1053/j.gastro.2018.11.018
Beeghly-Fadiel A, Wilson AJ, Keene S, et al. Differential cyclooxygenase expression levels and survival associations in type I and type II ovarian tumors. J Ovarian Res. 2018;11:17. doi:10.1186/s13048-018-0389-9
Banales JM, Sáez E, Úriz M, et al. Up-regulation of microRNA 506 leads to decreased cl-/HCO3- anion exchanger 2 expression in biliary epithelium of patients with primary biliary cirrhosis. Hepatology. 2012;56:687-697. doi:10.1002/hep.25691
Grubman SA, Perrone RD, Lee DW, et al. Regulation of intracellular pH by immortalized human intrahepatic biliary epithelial cell lines. Am J Physiol. 1994;266:G1060-1070. doi:10.1152/ajpgi.1994.266.6.G1060
Riccardi C, Nicoletti I. Analysis of apoptosis by propidium iodide staining and flow cytometry. Nat Protoc. 2006;1:1458-1461. doi:10.1038/nprot.2006.238
Hothorn TLB. On the exact distribution of maximally selected rank statistics. Comput Stat Data Anal. 2003;43:121-137. doi:10.1016/S0167-9473(02)00225-6
Abou-Alfa GK, Sahai V, Hollebecque A, et al. Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma: a multicentre, open-label, phase 2 study. Lancet Oncol. 2020;21:671-684. doi:10.1016/S1470-2045(20)30109-1
Abou-Alfa GK, Macarulla T, Javle MM, et al. Ivosidenib in IDH1-mutant, chemotherapy-refractory cholangiocarcinoma (ClarIDHy): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2020;21:796-807. doi:10.1016/S1470-2045(20)30157-1
Okaro AC, Deery AR, Hutchins RR, Davidson BR. The expression of antiapoptotic proteins Bcl-2, Bcl-X(L), and Mcl-1 in benign, dysplastic, and malignant biliary epithelium. J Clin Pathol. 2001;54:927-932. doi:10.1136/jcp.54.12.927
Charlotte F, L'Herminé A, Martin N, et al. Immunohistochemical detection of bcl-2 protein in normal and pathological human liver. Am J Pathol. 1994;144:460-465.
Skopelitou A, Hadjiyannakis M, Alexopoulou V, Krikoni O, Kamina S, Agnantis N. Topographical immunohistochemical expression of bcl-2 protein in human liver lesions. Anticancer Res. 1996;16:975-978.
Harnois DM, Que FG, Celli A, LaRusso NF, Gores GJ. Bcl-2 is overexpressed and alters the threshold for apoptosis in a cholangiocarcinoma cell line. Hepatology. 1997;26:884-890. doi:10.1002/hep.510260413
Ross JS, Wang K, Gay L, et al. New routes to targeted therapy of intrahepatic cholangiocarcinomas revealed by next-generation sequencing. Oncologist. 2014;19:235-242. doi:10.1634/theoncologist.2013-0352
Li S, Guo W, Wu H. The role of post-translational modifications in the regulation of MCL1. Cell Signal. 2021;81:109933. doi:10.1016/j.cellsig.2021.109933
Onyeagucha B, Subbarayalu P, Abdelfattah N, et al. Novel post-transcriptional and post-translational regulation of pro-apoptotic protein BOK and anti-apoptotic protein Mcl-1 determine the fate of breast cancer cells to survive or die. Oncotarget. 2017;8:85984-85996. doi:10.18632/oncotarget.20841
Bobo C, Céré C, Dufossée M, et al. Improved electrophoretic separation to assist the monitoring of Bcl-xL post-translational modifications. Int J Mol Sci. 2019;20:5571. doi:10.3390/ijms20225571
Follis AV, Llambi F, Kalkavan H, et al. Regulation of apoptosis by an intrinsically disordered region of Bcl-xL. Nat Chem Biol. 2018;14:458-465. doi:10.1038/s41589-018-0011-x
Zucchini N, de Sousa G, Bailly-Maitre B, et al. Regulation of Bcl-2 and Bcl-xL anti-apoptotic protein expression by nuclear receptor PXR in primary cultures of human and rat hepatocytes. Biochim Biophys Acta. 2005;1745:48-58. doi:10.1016/j.bbamcr.2005.02.005
Konig SM, Rissler V, Terkelsen T, Lambrughi M, Papaleo E. Alterations of the interactome of Bcl-2 proteins in breast cancer at the transcriptional, mutational and structural level. PLoS Comput Biol. 2019;15:e1007485. doi:10.1371/journal.pcbi.1007485
Weeden CE, Ah-Cann C, Holik AZ, et al. Dual inhibition of BCL-XL and MCL-1 is required to induce tumour regression in lung squamous cell carcinomas sensitive to FGFR inhibition. Oncogene. 2018;37:4475-4488. doi:10.1038/s41388-018-0268-2
Williams MM, Elion DL, Rahman B, Hicks DJ, Sanchez V, Cook RS. Therapeutic inhibition of Mcl-1 blocks cell survival in estrogen receptor-positive breast cancers. Oncotarget. 2019;10:5389-5402. doi:10.18632/oncotarget.27070
Yasuda Y, Ozasa H, Kim YH, et al. MCL1 inhibition is effective against a subset of small-cell lung cancer with high MCL1 and low BCL-XL expression. Cell Death Dis. 2020;11:177. doi:10.1038/s41419-020-2379-2
Wang W, Zhan M, Li Q, et al. FXR agonists enhance the sensitivity of biliary tract cancer cells to cisplatin via SHP dependent inhibition of Bcl-xL expression. Oncotarget. 2016;7:34617-34629. doi:10.18632/oncotarget.8964
Wu X, Luo Q, Liu Z. Ubiquitination and deubiquitination of MCL1 in cancer: deciphering chemoresistance mechanisms and providing potential therapeutic options. Cell Death Dis. 2020;11:556. doi:10.1038/s41419-020-02760-y
Wood KC. Overcoming MCL-1-driven adaptive resistance to targeted therapies. Nat Commun. 2020;11:531. doi:10.1038/s41467-020-14392-z
Bose P, Gandhi V, Konopleva M. Pathways and mechanisms of venetoclax resistance. Leuk Lymphoma. 2017;58:1-17. doi:10.1080/10428194.2017.1283032
Wang Q, Wan J, Zhang W, Hao S. MCL-1 or BCL-xL-dependent resistance to the BCL-2 antagonist (ABT-199) can be overcome by specific inhibitor as single agents and in combination with ABT-199 in acute myeloid leukemia cells. Leuk Lymphoma. 2019;60:2170-2180. doi:10.1080/10428194.2018.1563694
Josefsson EC, Vainchenker W, James C. Regulation of platelet production and life span: role of Bcl-xL and potential implications for human platelet diseases. Int J Mol Sci. 2020;21:7591. doi:10.3390/ijms21207591
Khan S, Zhang X, Lv D, et al. A selective BCL-XL PROTAC degrader achieves safe and potent antitumor activity. Nat Med. 2019;25:1938-1947. doi:10.1038/s41591-019-0668-z
Afreen S, Bohler S, Müller A, et al. BCL-XL expression is essential for human erythropoiesis and engraftment of hematopoietic stem cells. Cell Death Dis. 2020;11:8. doi:10.1038/s41419-019-2203-z
Mukherjee N, Skees J, Todd KJ, et al. MCL1 inhibitors S63845/MIK665 plus navitoclax synergistically kill difficult-to-treat melanoma cells. Cell Death Dis. 2020;11:443. doi:10.1038/s41419-020-2646-2
Sjostrom J, Blomqvist C, von Boguslawski K, et al. The predictive value of bcl-2, bax, bcl-xL, bag-1, fas, and fasL for chemotherapy response in advanced breast cancer. Clin Cancer Res. 2002;8:811-816.
Dunne PD, Coleman HG, Bankhead P, et al. Bcl-xL as a poor prognostic biomarker and predictor of response to adjuvant chemotherapy specifically in BRAF-mutant stage II and III colon cancer. Oncotarget. 2018;9:13834-13847. doi:10.18632/oncotarget.24481
Ben-Hamo R, Jacob Berger A, Gavert N, et al. Predicting and affecting response to cancer therapy based on pathway-level biomarkers. Nat Commun. 2020;11:3296. doi:10.1038/s41467-020-17090-y
Jin-Song Y, Zhao-Xia W, Cheng-Yu L, et al. Prognostic significance of Bcl-xL gene expression in human colorectal cancer. Acta Histochem. 2011;113:810-814. doi:10.1016/j.acthis.2011.01.002
Groeger AM, Esposito V, de Luca A, et al. Prognostic value of immunohistochemical expression of p53, bax, Bcl-2 and Bcl-xL in resected non-small-cell lung cancers. Histopathology. 2004;44:54-63. doi:10.1111/j.1365-2559.2004.01750.x
Addeo R, Caraglia M, Baldi A, et al. Prognostic role of bcl-xL and p53 in childhood acute lymphoblastic leukemia (ALL). Cancer Biol Ther. 2005;4:32-38. doi:10.4161/cbt.4.1.1371
Friess H, Lu Z, Andrén-Sandberg Å, et al. Moderate activation of the apoptosis inhibitor bcl-xL worsens the prognosis in pancreatic cancer. Ann Surg. 1998;228:780-787. doi:10.1097/00000658-199812000-00009
Jusakul A, Cutcutache I, Yong CH, et al. Whole-genome and epigenomic landscapes of etiologically distinct subtypes of cholangiocarcinoma. Cancer Discov. 2017;7:1116-1135. doi:10.1158/2159-8290.CD-17-0368
Nakamura H, Arai Y, Totoki Y, et al. Genomic spectra of biliary tract cancer. Nat Genet. 2015;47:1003-1010. doi:10.1038/ng.3375
Akita M, Sofue K, Fujikura K, et al. Histological and molecular characterization of intrahepatic bile duct cancers suggests an expanded definition of perihilar cholangiocarcinoma. HPB (Oxford). 2019;21:226-234. doi:10.1016/j.hpb.2018.07.021
Lowery MA, Ptashkin R, Jordan E, et al. Comprehensive molecular profiling of intrahepatic and extrahepatic Cholangiocarcinomas: potential targets for intervention. Clin Cancer Res. 2018;24:4154-4161. doi:10.1158/1078-0432.CCR-18-0078
Kendall T, Verheij J, Gaudio E, et al. Anatomical, histomorphological and molecular classification of cholangiocarcinoma. Liver Int. 2019;39(Suppl 1):7-18. doi:10.1111/liv.14093
Arai Y, Totoki Y, Hosoda F, et al. Fibroblast growth factor receptor 2 tyrosine kinase fusions define a unique molecular subtype of cholangiocarcinoma. Hepatology. 2014;59:1427-1434. doi:10.1002/hep.26890
Kipp BR, Voss JS, Kerr SE, et al. Isocitrate dehydrogenase 1 and 2 mutations in cholangiocarcinoma. Hum Pathol. 2012;43:1552-1558. doi:10.1016/j.humpath.2011.12.007
Rizzo A. Targeted therapies in advanced cholangiocarcinoma: a focus on FGFR inhibitors. Medicina (Kaunas). 2021;57:458. doi:10.3390/medicina57050458
Goyal L, Kongpetch S, Crolley VE, Bridgewater J. Targeting FGFR inhibition in cholangiocarcinoma. Cancer Treat Rev. 2021;95:102170. doi:10.1016/j.ctrv.2021.102170
Hoyos S, Navas MC, Restrepo JC, Botero RC. Current controversies in cholangiocarcinoma. Biochim Biophys Acta Mol Basis Dis. 2018;1864:1461-1467. doi:10.1016/j.bbadis.2017.07.027

Auteurs

Paula Hoffmeister-Wittmann (P)

Department of Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg, University Hospital Heidelberg, Heidelberg, Germany.
Department of Radiooncology, University Hospital Heidelberg, Heidelberg, Germany.

Andreas Mock (A)

Department of Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg, University Hospital Heidelberg, Heidelberg, Germany.
Department of Translational Medical Oncology, NCT Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany.
German Cancer Consortium (DKTK), Heidelberg and Partner Sites, Heidelberg, Germany.
Institute of Pathology, Medical Faculty, Ludwig-Maximilians-University, Munich, Germany.

Federico Nichetti (F)

Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy.
Computational Oncology Group, Molecular Precision Oncology Program, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), Heidelberg, Germany.

Felix Korell (F)

German Cancer Consortium (DKTK), Heidelberg and Partner Sites, Heidelberg, Germany.
Department of Medicine V, University Hospital Heidelberg, Heidelberg, Germany.

Christoph E Heilig (CE)

Department of Translational Medical Oncology, NCT Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany.
German Cancer Consortium (DKTK), Heidelberg and Partner Sites, Heidelberg, Germany.

Anna-Lena Scherr (AL)

Department of Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg, University Hospital Heidelberg, Heidelberg, Germany.

Michael Günther (M)

German Cancer Consortium (DKTK), Heidelberg and Partner Sites, Heidelberg, Germany.
Institute of Pathology, Medical Faculty, Ludwig-Maximilians-University, Munich, Germany.

Thomas Albrecht (T)

Institute for Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Liver Cancer Center Heidelberg, University Hospital Heidelberg, Heidelberg, Germany.

Eblina Kelmendi (E)

Department of Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg, University Hospital Heidelberg, Heidelberg, Germany.

Kaiyu Xu (K)

Department of Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg, University Hospital Heidelberg, Heidelberg, Germany.

Luisa Nader (L)

Department of Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg, University Hospital Heidelberg, Heidelberg, Germany.

Annika Kessler (A)

Department of Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg, University Hospital Heidelberg, Heidelberg, Germany.

Nathalie Schmitt (N)

Department of Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg, University Hospital Heidelberg, Heidelberg, Germany.

Sarah Fritzsche (S)

Institute for Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Liver Cancer Center Heidelberg, University Hospital Heidelberg, Heidelberg, Germany.

Sofia Weiler (S)

Institute for Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Liver Cancer Center Heidelberg, University Hospital Heidelberg, Heidelberg, Germany.

Benjamin Sobol (B)

Department of Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg, University Hospital Heidelberg, Heidelberg, Germany.

Albrecht Stenzinger (A)

Institute for Pathology, University Hospital Heidelberg, Heidelberg, Germany.

Stefan Boeck (S)

German Cancer Consortium (DKTK), Heidelberg and Partner Sites, Heidelberg, Germany.
Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Munich, Germany.

Christoph B Westphalen (CB)

German Cancer Consortium (DKTK), Heidelberg and Partner Sites, Heidelberg, Germany.
Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Munich, Germany.

Klaus Schulze-Osthoff (K)

German Cancer Consortium (DKTK), Heidelberg and Partner Sites, Heidelberg, Germany.
Department of Molecular Medicine, Interfaculty Institute for Biochemistry, University of Tübingen, Tübingen, Germany.

Jörg Trojan (J)

German Cancer Consortium (DKTK), Heidelberg and Partner Sites, Heidelberg, Germany.
Department of Gastroenterology, Gastrointestinal Medical Oncology, University Hospital Frankfurt, Frankfurt am Main, Germany.

Thomas Kindler (T)

German Cancer Consortium (DKTK), Heidelberg and Partner Sites, Heidelberg, Germany.
University Cancer Center, University Medical Center Mainz, Germany.

Wilko Weichert (W)

German Cancer Consortium (DKTK), Heidelberg and Partner Sites, Heidelberg, Germany.
Institute of Pathology, Medical Faculty, Technichal University Munich, Munich, Germany.

Karsten Spiekermann (K)

Department of Translational Medical Oncology, NCT Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany.
German Cancer Consortium (DKTK), Heidelberg and Partner Sites, Heidelberg, Germany.
Department of Hematology and Medical Oncology, University Hospital Munich, Ludwig-Maximilians-University of Munich, Munich, Germany.

Michael Bitzer (M)

German Cancer Consortium (DKTK), Heidelberg and Partner Sites, Heidelberg, Germany.
Department of Internal Medicine I, University Hospital Tübingen, Tübingen, Germany.

Gunnar Folprecht (G)

German Cancer Consortium (DKTK), Heidelberg and Partner Sites, Heidelberg, Germany.
Department of Hematology and Medical Oncology, Carl Gustav Carus University Hospital, Dresden, Germany.

Anna L Illert (AL)

German Cancer Consortium (DKTK), Heidelberg and Partner Sites, Heidelberg, Germany.
Department of Internal Medicine I, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Comprehensive Cancer Center Freiburg (CCCF), Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Melanie Boerries (M)

German Cancer Consortium (DKTK), Heidelberg and Partner Sites, Heidelberg, Germany.
Comprehensive Cancer Center Freiburg (CCCF), Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Institute of Medical Bioinformatics and Systems Medicine, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Frederick Klauschen (F)

German Cancer Consortium (DKTK), Heidelberg and Partner Sites, Heidelberg, Germany.
Institute of Pathology, Charité University Medicine Berlin, Berlin, Germany.

Sebastian Ochsenreither (S)

German Cancer Consortium (DKTK), Heidelberg and Partner Sites, Heidelberg, Germany.
Faculty of Medicine, Charité Comprehensive Cancer Center (CCCC), Humboldt University of Berlin, Berlin, Germany.
Department of hematology, medical oncology and tumor immunology, Charité University Medicine Berlin, Berlin, Germany.

Jens Siveke (J)

German Cancer Consortium (DKTK), Heidelberg and Partner Sites, Heidelberg, Germany.
Bridge Institute of Experimental Tumor Therapy, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Division of Solid Tumor Translational Oncology, German Cancer Consortium (DKTK Partner Site Essen) and German Cancer Research Center, DKFZ, Heidelberg, Germany.

Sebastian Bauer (S)

German Cancer Consortium (DKTK), Heidelberg and Partner Sites, Heidelberg, Germany.
Department for Translational Oncology, West German Tumor Center (WTZ), Essen University Hospital, Essen, Germany.

Hanno Glimm (H)

Translational Medical Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Department for Translational Medical Oncology, National Center for Tumor Diseases (NCT/UCC), Dresden, Germany: Germany Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, Germany.
German Cancer Consortium (DKTK) Dresden, Germany.
Translational Functional Cancer Genomics, National Center für Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), Heidelberg, Germany.

Benedikt Brors (B)

Computational Oncology Group, Molecular Precision Oncology Program, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), Heidelberg, Germany.

Jennifer Hüllein (J)

Computational Oncology Group, Molecular Precision Oncology Program, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), Heidelberg, Germany.

Daniel Hübschmann (D)

German Cancer Consortium (DKTK), Heidelberg and Partner Sites, Heidelberg, Germany.
Computational Oncology Group, Molecular Precision Oncology Program, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Heidelberg Institute for Stem cell Technology and Experimental Medicine (HI-STEM), Heidelberg, Germany.

Sebastian Uhrig (S)

Computational Oncology Group, Molecular Precision Oncology Program, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), Heidelberg, Germany.

Peter Horak (P)

Department of Translational Medical Oncology, NCT Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany.
German Cancer Consortium (DKTK), Heidelberg and Partner Sites, Heidelberg, Germany.

Simon Kreutzfeldt (S)

Department of Translational Medical Oncology, NCT Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany.
German Cancer Consortium (DKTK), Heidelberg and Partner Sites, Heidelberg, Germany.

Jesus M Banales (JM)

Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Ikerbasque, Network Centre for Biomedical Research in Liver and Digestive Diseases (CIBERehd), San Sebastian, Spain.
Department of Biochemistry and Genetics, School of Sciences, University of Navarra, Pamplona, Spain.

Christoph Springfeld (C)

Department of Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg, University Hospital Heidelberg, Heidelberg, Germany.

Dirk Jäger (D)

Department of Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg, University Hospital Heidelberg, Heidelberg, Germany.

Peter Schirmacher (P)

Institute for Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Liver Cancer Center Heidelberg, University Hospital Heidelberg, Heidelberg, Germany.

Stephanie Roessler (S)

Institute for Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Liver Cancer Center Heidelberg, University Hospital Heidelberg, Heidelberg, Germany.

Steffen Ormanns (S)

German Cancer Consortium (DKTK), Heidelberg and Partner Sites, Heidelberg, Germany.
Institute of Pathology, Medical Faculty, Ludwig-Maximilians-University, Munich, Germany.

Benjamin Goeppert (B)

Institute for Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Liver Cancer Center Heidelberg, University Hospital Heidelberg, Heidelberg, Germany.
Institute of Pathology and Neuropathology, RKH Klinikum Ludwigsburg, Ludwigsburg, Germany.

Stefan Fröhling (S)

Department of Translational Medical Oncology, NCT Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany.
German Cancer Consortium (DKTK), Heidelberg and Partner Sites, Heidelberg, Germany.

Bruno C Köhler (BC)

Department of Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg, University Hospital Heidelberg, Heidelberg, Germany.
German Cancer Consortium (DKTK), Heidelberg and Partner Sites, Heidelberg, Germany.
Liver Cancer Center Heidelberg, University Hospital Heidelberg, Heidelberg, Germany.

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