The M3 Research Center
Malignome, Metabolome and Microbiome

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. The molecular interaction pattern of lenvatinib enables inhibition of wild-type or kinase-mutated FGFR2-driven cholangiocarcinoma.

Nat Commun. 2024 Feb 12;15(1):1287. doi: 10.1038/s41467-024-45247-6. PMID: 38346946; PMCID: PMC10861557.

https://doi.org/10.1038/s41467-024-45247-6

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. Nivolumab and ipilimumab in recurrent or refractory cancer of unknown primary: a phase II trial.

Nat Commun. 2023 Oct 24;14(1):6761. doi: 10.1038/s41467-023-42400-5. PMID: 37875494; PMCID: PMC10598029. https://doi.org/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. BRAFΔβ3-αC in-frame deletion mutants differ in their dimerization propensity, HSP90 dependence, and druggability.

Sci Adv. 2023 Sep;9(35):eade7486. doi: 10.1126/sciadv.ade7486. Epub 2023 Sep 1. PMID: 37656784; PMCID: PMC11804575. https://doi.org/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. The German Network for Personalized Medicine to enhance patient care and translational research.

Nat Med. 2023 Jun;29(6):1298-1301. doi: 10.1038/s41591-023-02354-z. PMID: 37280276. https://doi.org/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. 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.

J Cancer Res Clin Oncol. 2023 Aug;149(9):5937-5950. doi: 10.1007/s00432-022-04459-3. Epub 2023 Jan 6. PMID: 36607429; PMCID: PMC10356865. https://doi.org/10.1007/s00432-022-04459-3

S3-Leitlinie: Diagnostik und Therapie biliärer Karzinome

Bitzer M, Voesch S, Albert J, Bartenstein P, Bechstein W, Blödt S, Brunner T, Dombrowski F, Evert M, Follmann M, La Fougère C, Freudenberger P, Geier A, Gkika E, Götz M, Hammes E, Helmberger T, Hoffmann RT, Hofmann WP, Huppert P, Kautz A, Knötgen G, Körber J, Krug D, Lammert F, Lang H, Langer T, Lenz P, Mahnken A, Meining A, Micke O, Nadalin S, Nguyen HP, Ockenga J, Oldhafer K, Paprottka P, Paradies K, Pereira P, Persigehl T, Plauth M, Plentz R, Pohl J, Riemer J, Reimer P, Ringwald J, Ritterbusch U, Roeb E, Schellhaas B, Schirmacher P, Schmid I, Schuler A, von Schweinitz D, Seehofer D, Sinn M, Stein A, Stengel A, Steubesand N, Stoll C, Tannapfel A, Taubert A, Trojan J, van Thiel I, Tholen R, Vogel A, Vogl T, Vorwerk H, Wacker F, Waidmann O, Wedemeyer H, Wege H, Wildner D, Wittekind C, Wörns MA, Galle P, Malek N. S3-Leitlinie: Diagnostik und Therapie biliärer Karzinome.

Z Gastroenterol. 2022 Feb;60(2):219-238. German. doi: 10.1055/a-1589-7638. Epub 2022 Feb 11. PMID: 35148562. https://doi.org/10.1055/a-1589-7638

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. Germline findings in patients with advanced malignancies screened with paired blood-tumour testing for personalised treatment approaches.

Eur J Cancer. 2023 Jan;179:48-55. doi: 10.1016/j.ejca.2022.11.003. Epub 2022 Nov 8. PMID: 36495689. https://doi.org/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. The oncogenic fusion protein DNAJB1-PRKACA can be specifically targeted by peptide-based immunotherapy in fibrolamellar hepatocellular carcinoma.

Nat Commun. 2022 Oct 27;13(1):6401. doi: 10.1038/s41467-022-33746-3. PMID: 36302754; PMCID: PMC9613889. https://doi.org/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; GMS working group and ZPM working group. Trailblazing precision medicine in Europe: A joint view by Genomic Medicine Sweden and the Centers for Personalized Medicine, ZPM, in Germany.

Semin Cancer Biol. 2022 Sep;84:242-254. doi: 10.1016/j.semcancer.2021.05.026. Epub 2021 May 24. PMID: 34033893. https://doi.org/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. Preexisting comorbidities shape the immune response associated with severe COVID-19.

J Allergy Clin Immunol. 2022 Aug;150(2):312-324. doi: 10.1016/j.jaci.2022.05.019. Epub 2022 Jun 16. PMID: 35716951; PMCID: PMC9212690. https://doi.org/10.1016/j.jaci.2022.05.019

S3-Leitlinie: Diagnostik und Therapie des hepatozellulären Karzinoms und biliärer Karzinome – Version 2.0 – Juni 2021, AWMF-Registernummer: 032-053OL

Voesch S, Bitzer M, Blödt S, Follmann M, Freudenberger P, Langer T, Lorenz P, Jansen PL, Steubesand N, Galle P, Malek N. S3-Leitlinie: Diagnostik und Therapie des hepatozellulären Karzinoms und biliärer Karzinome – Version 2.0 – Juni 2021, AWMF-Registernummer: 032-053OL.

Z Gastroenterol. 2022 Jan;60(1):e131-e185. German. doi: 10.1055/a-1589-7585. Epub 2022 Jan 18. PMID: 35042250. https://doi.org/10.1055/a-1589-7585

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. Distinct immunological signatures discriminate severe COVID-19 from non-SARS-CoV-2-driven critical pneumonia.

Immunity. 2021 Jul 13;54(7):1578-1593.e5. doi: 10.1016/j.immuni.2021.05.002. Epub 2021 May 9. Erratum in: Immunity. 2022 Feb 8;55(2):366-375. doi: 10.1016/j.immuni.2022.01.015. PMID: 34051147; PMCID: PMC8106882. https://doi.org/10.1016/j.immuni.2021.05.002

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. 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.

Lancet Gastroenterol Hepatol. 2021 Oct;6(10):803-815. doi: 10.1016/S2468-1253(21)00196-5. Epub 2021 Aug 3. PMID: 34358484. https://doi.org/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. Targeting extracellular and juxtamembrane FGFR2 mutations in chemotherapy-refractory cholangiocarcinoma.

NPJ Precis Oncol. 2021 Sep 3;5(1):80. doi: 10.1038/s41698-021-00220-0. PMID: 34480077; PMCID: PMC8417271. https://doi.org/10.1038/s41698-021-00220-0

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; COVID-19 Aachen Study (COVAS); 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; Deutsche COVID-19 Omics Initiative (DeCOI); Breteler MMB, Giamarellos-Bourboulis EJ, Kox M, Becker M, Cheran S, Woodacre MS, Goh EL, Schultze JL. Swarm Learning for decentralized and confidential clinical machine learning.

Nature. 2021 Jun;594(7862):265-270. doi: 10.1038/s41586-021-03583-3. Epub 2021 May 26. PMID: 34040261; PMCID: PMC8189907. https://doi.org/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. NASH limits anti-tumour surveillance in immunotherapy-treated HCC.

Nature. 2021 Apr;592(7854):450-456. doi: 10.1038/s41586-021-03362-0. Epub 2021 Mar 24. PMID: 33762733; PMCID: PMC8046670. https://doi.org/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. Clinical and Genetic Tumor Characteristics of Responding and Non-Responding Patients to PD-1 Inhibition in Hepatocellular Carcinoma. 

Cancers (Basel). 2020 Dec 18;12(12):3830. doi: 10.3390/cancers12123830. PMID: 33353145; PMCID: PMC7766321. https://doi.org/10.3390/cancers12123830

Next-Generation Sequencing of Advanced GI Tumors Reveals Individual Treatment Options

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. Next-Generation Sequencing of Advanced GI Tumors Reveals Individual Treatment Options. 

JCO Precis Oncol. 2020 Mar 30;4:PO.19.00359. doi: 10.1200/PO.19.00359. PMID: 32923905; PMCID: PMC7446530. https://doi.org/10.1200/po.19.00359