Gastrointestinal Oncology and Personalized Medicine

Our group engages in both translational and clinical research in gastrointestinal oncology and personalized medicine. In the realm of translational research, our focus lies on targeted therapies for cancer, exploring novel approaches or combination treatments and clinical studies. Main topics within the last few years have been FGFR2-driven liver tumors, ADORA3-targeting in liver cancer, molecular tumor analysis to guide treatment decisions, and the investigation of exceptional responders or non-responders after Molecular Tumorboard guided treatments. By conducting both translational and clinical research, we aim to advance our understanding of gastrointestinal oncology and develop innovative strategies for improving the diagnosis and treatment of cancer in the gastrointestinal tract.

Michael Bitzer is Vice Director of the Department of Internal Medicine I, Head of Gastrointestinal Oncology and the Molecular Tumorboard at Tübingen University Hospital. He is one of the current coordinators of the German S3 guideline on liver cancer and spokesman for the working group "Harmonization of Molecular Tumor Boards" of ZPM Baden-Württemberg and the German Network for Personalized Medicine (DNPM).

Teamfoto
Our research team
ADORA3
targeting
FGFR2
driven liver tumors
molecular
tumor analysis

Selected publications

  • The molecular interaction pattern of lenvatinib enables inhibition of wild-type or kinase-mutated FGFR2-driven cholangiocarcinoma.
    Spahn S, Kleinhenz F, Shevchenko E, Stahl A, Rasen Y, Geisler C, Ruhm K, Klaumuenzer M, Kronenberger T, Laufer SA, Sundberg-Malek H, Bui KC, Horger M, Biskup S, Schulze-Osthoff K, Templin M, Malek NP, Poso A, Bitzer M.Nat Commun. 2024 Feb 12;15(1):1287. doi: 10.1038/s41467-024-45247-6.PMID: 38346946
  • Nivolumab and ipilimumab in recurrent or refractory cancer of unknown primary: a phase II trial.
     
    Pouyiourou M, Kraft BN, Wohlfromm T, Stahl M, Kubuschok B, Löffler H, Hacker UT, Hübner G, Weiss L, Bitzer M, Ernst T, Schütt P, Hielscher T, Delorme S, Kirchner M, Kazdal D, Ball M, Kluck K, Stenzinger A, Bochtler T, Krämer A.
     Nat Commun. 2023 Oct 24;14(1):6761. doi: 10.1038/s41467-023-42400-5.
  • BRAFΔβ3-αC in-frame deletion mutants differ in their dimerization propensity, HSP90 dependence, and druggability.
     
    Lauinger M, Christen D, Klar RFU, Roubaty C, Heilig CE, Stumpe M, Knox JJ, Radulovich N, Tamblyn L, Xie IY, Horak P, Forschner A, Bitzer M, Wittel UA, Boerries M, Ball CR, Heining C, Glimm H, Fröhlich M, Hübschmann D, Gallinger S, Fritsch R, Fröhling S, O'Kane GM, Dengjel J, Brummer T
     Sci Adv. 2023 Sep;9(35):eade7486. doi: 10.1126/sciadv.ade7486
  • The German Network for Personalized Medicine to enhance patient care and translational research.
     
    Illert AL, Stenzinger A, Bitzer M, Horak P, Gaidzik VI, Möller Y, Beha J, Öner Ö, Schmitt F, Laßmann S, Ossowski S, Schaaf CP, Hallek M, Brümmendorf TH, Albers P, Fehm T, Brossart P, Glimm H, Schadendorf D, Bleckmann A, Brandts CH, Esposito I, Mack E, Peters C, Bokemeyer C, Fröhling S, Kindler T, Algül H, Heinemann V, Döhner H, Bargou R, Ellenrieder V, Hillemanns P, Lordick F, Hochhaus A, Beckmann MW, Pukrop T, Trepel M, Sundmacher L, Wesselmann S, Nettekoven G, Kohlhuber F, Heinze O, Budczies J, Werner M, Nikolaou K, Beer AJ, Tabatabai G, Weichert W, Keilholz U, Boerries M, Kohlbacher O, Duyster J, Thimme R, Seufferlein T, Schirmacher P, Malek NP.
     Nat Med. 2023 Jun;29(6):1298-1301. doi: 10.1038/s41591-023-02354-z
  • Immunological effects and activity of multiple doses of zolbetuximab in combination with zoledronic acid and interleukin-2 in a phase 1 study in patients with advanced gastric and gastroesophageal junction cancer.
     
    Lordick F, Thuss-Patience P, Bitzer M, Maurus D, Sahin U, Türeci Ö.
     J Cancer Res Clin Oncol. 2023 Aug;149(9):5937-5950.
  • S3-Leitlinie Diagnostik und Therapie biliärer Karzinome
     Bitzer M
    , Groß S, Albert J, Boda-Heggemann J, Brunner T, Caspari R, De Toni E, Dombrowski F, Evert M, Geier A, Gkika E, Götz M, Helmberger T, Hoffmann RT, Huppert P, Kautz A, Krug D, Fougère C, Lang H, Lenz P, Lüdde T, Mahnken A, Nadalin S, Nguyen HHP, Ockenga J, Oldhafer K, Paprottka P, Pereira P, Persigehl T, Plentz R, Pohl J, Recken H, Reimer P, Riemer J, Ritterbusch U, Roeb E, Rüssel J, Schellhaas B, Schirmacher P, Schlitt HJ, Schmid I, Schuler A, Seehofer D, Sinn M, Stengel A, Stoll C, Tannapfel A, Taubert A, Tholen R, Trojan J, van Thiel I, Vogel A, Vogl T, Wacker F, Waidmann O, Wedemeyer H, Wege H, Wildner D, Wörns MA, Galle P, Malek N.
     Z Gastroenterol. 2023 Apr; 61(4):420-440. doi: 10.1055/a-2026-1277.
  • Germline findings in patients with advanced malignancies screened with paired blood-tumour testing for personalised treatment approaches.
     
    Roggia C, Armeanu-Ebinger S, Gschwind A, Seibel-Kelemen O, Hertler S, Faust U, Liebmann A, Haack TB, Neumann M, Bonzheim I, Forschner A, Kopp HG, Herster F, Hartkopf A, Bitzer M, Malek NP, Brecht IB, Ruhm K, Möller Y, Löwenheim H, Ossowski S, Rieß OH, Schroeder C.
     Eur J Cancer. 2023 Jan;179:48-55. doi: 10.1016/j.ejca.2022.11.003.
  • The oncogenic fusion protein DNAJB1-PRKACA can be specifically targeted by peptide-based immunotherapy in fibrolamellar hepatocellular carcinoma.
     
    Bauer J, Köhler N, Maringer Y, Bucher P, Bilich T, Zwick M, Dicks S, Nelde A, Dubbelaar M, Scheid J, Wacker M, Heitmann JS, Schroeder S, Rieth J, Denk M, Richter M, Klein R, Bonzheim I, Luibrand J, Holzer U, Ebinger M, Brecht IB, Bitzer M, Boerries M, Feucht J, Salih HR, Rammensee HG, Hailfinger S, Walz JS.
     Nat Commun. 2022 Oct 27;13(1):6401. doi: 10.1038/s41467-022-33746-3.
  • Trailblazing precision medicine in Europe: A joint view by Genomic Medicine Sweden and the Centers for Personalized Medicine, ZPM, in Germany.
     
    Stenzinger A, Edsjö A, Ploeger C, Friedman M, Fröhling S, Wirta V, Seufferlein T, Botling J, Duyster J, Akhras M, Thimme R, Fioretos T, Bitzer M, Cavelier L, Schirmacher P, Malek N, Rosenquist R.
     Semin Cancer Biol. 2022 Sep; 84:242-254. doi: 10.1016/j.semcancer.2021.05.026.
  • Preexisting comorbidities shape the immune response associated with severe COVID-19.
     
    Kreutmair S, Kauffmann M, Unger S, Ingelfinger F, Núñez NG, Alberti C, De Feo D, Krishnarajah S, Friebel E, Ulutekin C, Babaei S, Gaborit B, Lutz M, Jurado NP, Malek NP, Göpel S, Rosenberger P, Häberle HA, Ayoub I, Al-Hajj S, Claassen M*, Liblau R*, Martin-Blondel G*, Bitzer M*, Roquilly A*, Becher B*.
    J Allergy Clin Immunol. 2022 Aug;150(2):312-324. doi: 10.1016/j.jaci.2022.05.019.
    *shared senior authorship
  • S3-Leitlinie: Diagnostik und Therapie des hepatozellulären Karzinoms und biliärer Karzinome – Version 2.0 – Juni 2021
     
    Voesch S, Bitzer M, Blödt S, Follmann M, Freudenberger P, Langer T, Lorenz P, Jansen PL, Steubesand N, Galle P, Malek N.
     Z Gastroenterol. 2022 Jan;60(1):e131-e185. doi: 10.1055/a-1589-7585.
  • Infigratinib (BGJ398) in previously treated patients with advanced or metastatic cholangiocarcinoma with FGFR2 fusions or rearrangements: mature results from a multicentre, open-label, single-arm, phase 2 study.
     
    Javle M, Roychowdhury S, Kelley RK, Sadeghi S, Macarulla T, Weiss KH, Waldschmidt DT, Goyal L, Borbath I, El-Khoueiry A, Borad MJ, Yong WP, Philip PA, Bitzer M, Tanasanvimon S, Li A, Pande A, Soifer HS, Shepherd SP, Moran S, Zhu AX, Bekaii-Saab TS, Abou-Alfa GK.
     Lancet Gastroenterol Hepatol. 2021 Oct;6(10):803-815. doi: 10.1016/S2468-1253(21)00196-5.
  • Targeting extracellular and juxtamembrane FGFR2 mutations in chemotherapy-refractory cholangiocarcinoma.
     
    Bitzer M, Spahn S, Babaei S, Horger M, Singer S, Schulze-Osthoff K, Missios P, Gatidis S, Nann D, Mattern S, Scheble V, Nikolaou K, Armeanu-Ebinger S, Schulze M, Schroeder C, Biskup S, Beha J, Claassen M, Ruhm K, Poso A, Malek NP.
     NPJ Precis Oncol. 2021 Sep 3;5(1):80. doi: 10.1038/s41698-021-00220-0.
  • Distinct immunological signatures discriminate severe COVID-19 from non-SARS-CoV-2-driven critical pneumonia.
     
    Kreutmair S, Unger S, Núñez NG, Ingelfinger F, Alberti C, De Feo D, Krishnarajah S, Kauffmann M, Friebel E, Babaei S, Gaborit B, Lutz M, Jurado NP, Malek NP, Goepel S, Rosenberger P, Häberle HA, Ayoub I, Al-Hajj S, Nilsson J, Claassen M*, Liblau R*, Martin-Blondel G*, Bitzer M*, Roquilly A*, Becher B.*
    Immunity. 2021 Jul 13;54(7):1578-1593.e5. doi: 10.1016/j.immuni.2021.05.002.
    *shared senior authorship
  • Swarm Learning for decentralized and confidential clinical machine learning.
     
    Warnat-Herresthal S, Schultze H, Shastry KL, Manamohan S, Mukherjee S, Garg V, Sarveswara R, Händler K, Pickkers P, Aziz NA, Ktena S, Tran F, Bitzer M, Ossowski S, Casadei N, Herr C, Petersheim D, Behrends U, Kern F, Fehlmann T, Schommers P, Lehmann C, Augustin M, Rybniker J, Altmüller J, Mishra N, Bernardes JP, Krämer B, Bonaguro L, Schulte-Schrepping J, De Domenico E, Siever C, Kraut M, Desai M, Monnet B, Saridaki M, Siegel CM, Drews A, Nuesch-Germano M, Theis H, Heyckendorf J, Schreiber S, Kim-Hellmuth S, Nattermann J, Skowasch D, Kurth I, Keller A, Bals R, Nürnberg P, Rieß O, Rosenstiel P, Netea MG, Theis F, Mukherjee S, Backes M, Aschenbrenner AC, Ulas T, Breteler MMB, Giamarellos-Bourboulis EJ, Kox M, Becker M, Cheran S, Woodacre MS, Goh EL, Schultze JL.
     Nature. 2021 Jun;594(7862):265-270. doi: 10.1038/s41586-021-03583-3.
  • NASH limits anti-tumour surveillance in immunotherapy-treated HCC.
     
    Pfister D, Núñez NG, Pinyol R, Govaere O, Pinter M, Szydlowska M, Gupta R, Qiu M, Deczkowska A, Weiner A, Müller F, Sinha A, Friebel E, Engleitner T, Lenggenhager D, Moncsek A, Heide D, Stirm K, Kosla J, Kotsiliti E, Leone V, Dudek M, Yousuf S, Inverso D, Singh I, Teijeiro A, Castet F, Montironi C, Haber PK, Tiniakos D, Bedossa P, Cockell S, Younes R, Vacca M, Marra F, Schattenberg JM, Allison M, Bugianesi E, Ratziu V, Pressiani T, D'Alessio A, Personeni N, Rimassa L, Daly AK, Scheiner B, Pomej K, Kirstein MM, Vogel A, Peck-Radosavljevic M, Hucke F, Finkelmeier F, Waidmann O, Trojan J, Schulze K, Wege H, Koch S, Weinmann A, Bueter M, Rössler F, Siebenhüner A, De Dosso S, Mallm JP, Umansky V, Jugold M, Luedde T, Schietinger A, Schirmacher P, Emu B, Augustin HG, Billeter A, Müller-Stich B, Kikuchi H, Duda DG, Kütting F, Waldschmidt DT, Ebert MP, Rahbari N, Mei HE, Schulz AR, Ringelhan M, Malek N, Spahn S, Bitzer M, Ruiz de Galarreta M, Lujambio A, Dufour JF, Marron TU, Kaseb A, Kudo M, Huang YH, Djouder N, Wolter K, Zender L, Marche PN, Decaens T, Pinato DJ, Rad R, Mertens JC, Weber A, Unger K, Meissner F, Roth S, Jilkova ZM, Claassen M, Anstee QM, Amit I, Knolle P, Becher B, Llovet JM, Heikenwalder M.
     Nature. 2021 Apr;592(7854):450-456. doi: 10.1038/s41586-021-03362-0.
  • Clinical and Genetic Tumor Characteristics of Responding and Non-Responding Patients to PD-1 Inhibition in Hepatocellular Carcinoma.
     
    Spahn S, Roessler D, Pompilia R, Gabernet G, Gladstone BP, Horger M, Biskup S, Feldhahn M, Nahnsen S, Hilke FJ, Scheiner B, Dufour JF, De Toni EN, Pinter M, Malek NP, Bitzer M.
     Cancers (Basel). 2020 Dec 18;12(12). doi: 10.3390/cancers12123830
  • Next-Generation Sequencing of Advanced GI Tumors Reveals Individual Treatment Options.JCO Precis
     
    Bitzer M, Ostermann L, Horger M, Biskup S, Schulze M, Ruhm K, Hilke F, Öner Ö, Nikolaou K, Schroeder C, Riess O, Fend F, Zips D, Hinterleitner M, Zender L, Tabatabai G, Beha J, Malek NP.
    JCO Precis Oncol. 2020;4. doi: 10.1200/PO.19.00359.