NCT Heidelberg

Selected Publications

Tamborero D, Dienstmann R, Rachid MH, Boekel J, Baird R, Braña I, De Petris L, Yachnin J, Massard C, Opdam F, Schlenk R, Vernieri C, Garralda E, Masucci M, Villalobos X, Chavarria E, Cancer Core Europe consortium, Calvo F, Fröhling S, Eggermont A, Apolone G, Voest EE, Caldas C, Tabernero J, Ernberg I, Rodon J, Lehtiö J. Support systems to guide clinical decision-making in precision oncology: the Cancer Core Europe Molecular Tumor Board Portal. Nat Med 26:992-994, 2020.

Jensen P, Carlet M, Schlenk RF, Weber A, Kress J, Brunner I, Słabicki M, Grill G, Weisemann S, Cheng YY, Jeremias I, Scholl C,* Fröhling S.* Requirement for LIM kinases in acute myeloid leukemia. Leukemia. Accepted for publication.

  • These findings identify increased activity of the LIMK1 and LIMK2 kinases as crucial and potentially targetable feature in the development of acute myeloid leukemia.

Vu T, Straube J, Porter AH, Bywater M, Song A, Ling V, Cooper L, Pali G, Bruedigam C, Jacquelin S, Green J, Magor G, Perkins A, Chalk AM, Walkley CR, Heidel FH, Mukhopadhyay P, Cloonan N, Gröschel S, Mallm JP, Fröhling S, Scholl C, Lane SW. Hematopoietic stem and progenitor cell-restricted Cdx2 expression induces transformation to myelodysplasia and acute leukemia. Nat Commun 11:3021, 2020.

Heilig CE, Horak P, Lipka DB, Mock A, Uhrig S, Kreutzfeldt S, Richter S, Gieldon L, Fröhlich M, Hutter B, Hübschmann D, Teleanu V, Schmier JW, Philipzen J, Beuthien-Baumann B, Schröck E, von Deimling A, Bauer S, Heining C, Mechtersheimer G, Stenzinger A, Brors B, Wardelmann E, Glimm H,* Hartmann W,* Fröhling S.* Germline SDHB-inactivating mutation in gastric spindle cell sarcoma. Genes Chromosomes Cancer 59:601-608, 2020.

  • This work describes the loss of function of the succinate dehydrogenase complex based on a hereditary SDHB mutation in a patient with spindle cell sarcoma of the stomach.

Słabicki M, Kozicka Z, Petzold G, Li YD, Manojkumar M, Bunker R, Donovan KA, Sievers QL, Koeppel J, Suchyta D, Sperling AS, Gasser JA, Wang LR, Corsello SM, Sellar RS, Jan M, Fink EC, Gillingham D, Scholl C, Fröhling S, Golub TR, Fischer ES, Thomä NH, Ebert BL. The CDK inhibitor CR8 mediates cyclin K degradation through the CUL4-RBX1-DDB1 E3 ubiquitin ligase. Nature. Accepted for publication.

van de Haar J, Hoes LR, Coles CE, Seamon K, Fröhling S, Jäger D, Valenza F, de Braud F, De Petris L, Bergh J, Ernberg I, Besse B, Barlesi F, Garralda E, Piris-Giménez A, Baumann M, Apolone G, Soria JC, Tabernero J, Caldas C, Voest EE. Caring for cancer patients in the COVID-19 era. Nat Med 26:665-671, 2020.

Voronina N, Wong JKL, Hübschmann D, Hlevnjak M, Uhrig S, Heilig CE, Horak P, Kreutzfeldt S, Mock A, Stenzinger A, Hutter B, Fröhlich M, Brors B, Jahn A, Klink B, Gieldon L, Sieverling L, Feuerbach L, Chudasama P, Beck K, Kroiss M, Heining C, Möhrmann L, Fischer A, Schröck E, Glimm H, Zapatka M, Lichter P, Fröhling S, Ernst A. The landscape of chromothripsis across adult cancer types. Nat Commun 11:2320, 2020.

Ronellenfitsch MW, Harter PN, Kirchner M, Heining C, Hutter B, Gieldon L, Schittenhelm J, Schuhmann MU, Tatagiba M, Marquardt G, Wagner M, Endris V, Brandts CH, Mautner VF, Schröck E, Weichert W, Brors B, von Deimling A, Mittelbronn M, Steinbach JP,* Reuss DE,* Glimm H,* Stenzinger A,* Fröhling S.* Targetable ERBB2 mutations identified in neurofibroma/schwannoma hybrid nerve sheath tumors. J Clin Invest 130:2488-2495, 2020.

  • This work describes the discovery of activating mutations of the ERBB2 receptor as recurrent and therapeutically addressable changes in patients with hybrid tumors of the peripheral nervous system.

Mock A, Heilig CE, Kreutzfeldt S, Hübschmann D, Heining C, Schröck E, Brors B, Stenzinger A, DKTK MASTER Network, Jäger D, Schlenk RF, Glimm H, Fröhling,* Horak P.* Community-driven development of a modified progression-free survival ratio for precision oncology. ESMO Open 4:e000583, 2019.

  • This work describes a novel clinical endpoint that could aid in the design and interpretation of future precision oncology trials.

Weinberg F, Herr R, Fröhlich M, Heining C, Braun S, Spohr C, Iconomou M, Hollek V, Röring M, Horak P, Kreutzfeldt S, Warsow G, Hutter B, Uhrig S, Neumann O, Reuss D, Heiland DH, von Kalle C, Weichert W, Stenzinger A, Brors B, Glimm H,* Fröhling S,* Brummer T.* Identification and characterization of a BRAF fusion oncoprotein with retained autoinhibitory domains. Oncogene 39:814-832, 2020.

  • This work describes the first example of a fully autoinhibited BRAF protein whose oncogenic potential is dictated by a distinct fusion partner and not by a structural change in BRAF itself.

Gröschel S, Hübschmann D, Raimondi F, Horak P, Warsow G, Fröhlich M, Klink B, Gieldon L, Hutter B, Kleinheinz K, Bonekamp D, Marschal O, Chudasama P, Mika J, Groth M, Uhrig S, Krämer S, Heining C, Heilig CE, Richter D, Reisinger E, Pfütze K, Eils R, Wolf S, von Kalle C, Brandts C, Scholl C, Weichert W, Richter S, Bauer S, Penzel R, Schröck E, Stenzinger A, Schlenk RF, Brors B, Russell RB, Glimm H, Schlesner M, Fröhling S. Defective homologous recombination DNA repair as therapeutic target in advanced chordoma. Nat Commun 10:1635, 2019.

  • This work describes the discovery of defective homologous recombination DNA repair as therapeutic target in patients with advanced chordoma, and provides new insight into the mechanisms underlying acquired resistance to pharmacologic PARP inhibition.

Trautmann M, Cheng YY, Jensen P, Azoitei N, Brunner I, Hüllein J, Slabicki M, Isfort I, Cyra M, Wardelmann E, Huss S, Altvater B, Rossig C, Hafner S, Simmet T, Ståhlberg A, Åman P, Zenz T, Lange U, Kindler T, Scholl C, Hartmann W, Fröhling S. Requirement for YAP1 signaling in myxoid liposarcoma. EMBO Mol Med, accepted for publication.

  • These findings identify increased activity of the transcriptional co-activator YAP1 as crucial and potentially targetable feature in the development of myxoid liposarcoma.

Heining C, Horak, P, Uhrig S, Codó P, Klink B, Hutter B, Fröhlich M, Bonekamp D, Richter D, Steiger K, Penzel R, Endris V, Ehrenberg KR, Frank S, Kleinheinz K, Toprak UH, Schlesner M, Mandal R, Schulz L, Lambertz H, Fetscher S, Bitzer M, Malek NP, Horger M, Giese NA, Strobel O, Hackert T, Springfeld C, Feuerbach L, Bergmann F, Schröck E, von Kalle C, Weichert W, Scholl C, Ball CR, Stenzinger A, Brors B, Fröhling S,* Glimm H.* NRG1 fusions in KRAS wild-type pancreatic cancer. Cancer Discov 8:1087-1095, 2018.

  • This work describes the discovery of rearrangements of the NRG1 gene as recurrent and therapeutically addressable changes in young patients with advanced pancreatic cancer.

Chudasama P, Mughal SS, Sanders MA, Hübschmann D, Chung I, Deeg KI, Wong SH, Rabe S, Hlevnjak M, Zapatka M, Ernst A, Kleinheinz K, Schlesner M, Sieverling L, Klink B, Schröck E, Hoogenboezem RM, Kasper B, Heilig C, Egerer G, Wolf S, von Kalle C, Eils R, Stenzinger A, Weichert W, Glimm H, Gröschel S, Kopp HG, Omlor G, Lehner B, Bauer S, Schimmack S, Ulrich A, Mechtersheimer G, Rippe K, Brors B, Hutter B, Renner M, Hohenberger P, Scholl C, Fröhling S. Integrative genomic and transcriptomic analysis of leiomyosarcoma. Nat Commun 9:144, 2018.

  • This work describes the systematic analysis of the genetic “landscape” of advanced leiomyosarcoma. The results have provided the basis for the NCT PMO-1603 (TOP-ART) trial for patients with advanced solid tumors and defective homologous recombination DNA repair.

Dieter SM, Heining C, Agaimy A, Huebschmann D, Bonekamp D, Hutter B, Ehrenberg KR, Fröhlich M, Schlesner M, Scholl C, Schlemmer HP, Wolf S, Mavratzas A, Jung CS, Gröschel S, von Kalle C, Eils R, Brors B, Penzel R, Kriegsmann M, Reuss DE, Schirmacher P, Stenzinger A, Federspil PA, Weichert W,* Glimm H,* Fröhling S.* Mutant KIT as imatinib-sensitive target in metastatic sinonasal carcinoma. Ann Oncol 28:142-148, 2017.

  • This work describes an activating mutation of the KIT receptor in a patient with a sinonasal carcinoma as a cross-entity point of attack for therapy.

Chudasama P, Renner M, Straub M, Mughal SS, Hutter B, Kosaloglu Z, Schweßinger R, Scheffler M, Alldinger I, Schimmack S, Persigehl T, Kobe C, Jäger D, von Kalle C, Schirmacher P, Beckhaus MK, Wolf S, Heining C, Gröschel S, Wolf J, Brors B, Weichert W, Glimm H, Scholl C, Mechtersheimer G, Specht K, Fröhling S. Targeting FGFR1 for treatment of soft-tissue sarcoma. Clin Cancer Res 23:962-973, 2017.

  • This work describes the discovery of recurrent changes of the FGFR1 receptor as a therapeutic target in patients with soft-tissue sarcomas.

Kordes M, Röring M, Heining C, Braun S, Hutter B, Richter D, Geörg C, Scholl C, Gröschel S, Roth W, Rosenwald A, Geissinger E, von Kalle C, Jäger D, Brors B, Weichert W, Grüllich C, Glimm H,* Brummer T,* Fröhling S.* Cooperation of BRAF F595L and mutant HRAS in histiocytic sarcoma provides new insights into oncogenic BRAF signaling. Leukemia 30:937-946, 2016.

  • This work describes a new and therapeutically addressable class of activating mutations of the BRAF kinase.

Placke T, Faber K, Nonami A, Putwain SL, Salih HR, Heidel FH, Krämer A, Root DE, Barbie DA, Krivtsov AV, Armstrong SA, Hahn WC, Huntly BJ, Sykes SM, Milsom MD, Scholl C,* Fröhling S.* Requirement for CDK6 in MLL-rearranged acute myeloid leukemia. Blood 124:13-23, 2014.

  • This work describes the discovery of the cell cycle regulator CDK6 as a therapeutically addressable effector of MLL fusion proteins in an aggressive subtype of acute myeloid leukemia. The results have provided the basis for the AMLSG 23-14 trial of the German Austrian AML Study Group.