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Department for Translational Medical Oncology

The Department for Translational Medical Oncology investigates the molecular and cellular mechanisms for cancer development, proliferation and evolution. The department engages in clinical as well as experimental activities to ensure a rapid turnaround of scientific results into clinical application and clinical outcome into new hypotheses. Experimentally, high-throughput, multi-parametric molecular profiling is used to discover differences in the genome of tumor and normal cells to identify novel targets for cancer therapy on the genomic or cellular level.

The group develops suitable model systems to functionally and mechanistically characterize their impact and assess the potential for clinical application. Clinically, a dedicated personalized oncology outpatient clinic provides consulting appointments to initiate innovative diagnostic approaches, and organizes a tumor board to discuss results of genetic tumor profiling and molecularly guided treatment strategies.

Understanding and targeting alterations in cancer

Unique alterations within tumor cells can be targets for novel treatment approaches. Scientists of the department for Translational Medical Oncology are working on identifying pivotal gene alterations and cellular subtypes that are responsible for initiating or fueling tumor growth and metastasis formation. Within individual patient tumors, a small fraction of all cells drives long-term tumor growth and metastases. Targeting this tumor-initiating cells (TIC) activity is essential to improve the long-term outcome in advanced solid cancers. The lab has developed and extensively characterized a bank of primary in vitro and in vivo models derived from solid patient tumors, e.g. CRC, PDAC and sarcomas. These functionally and genetically heterogeneous models are utilized to identify therapy relevant alterations and synthetic lethal interactions, e.g. by large scale shRNA knockdown or overexpression screening approaches. Following functional testing of potential therapeutic target alterations, targeted therapeutic strategies are developed and translated into the clinic.

The Glimm Lab, represented by the Department of Translational Medical Oncology in Dresden and the Translational Functional Cancer Genomics group in Heidelberg, welcomes researchers at both NCT partner sites to join their expertise in collaborating on these research questions.

Dr. Claudia Ball
Senior Scientist, Head of Laboratory
Email: claudia.ball(at)nct-dresden.de

NCT MASTER Registry trial for patients

In an interdisciplinary approach, new discoveries are directly transferred into treatment recommendations using the NCT/DKTK MASTER registry trial. The NCT-MASTER (Molecularly Aided Stratification for Tumor Eradication) protocol consents young patients or patients with rare tumor diseases for molecular diagnostics approaches with the explicit purpose of evaluating and stratifying for the best molecular treatment strategy and enrolment in diagnostic and therapeutic clinical trials. The NCT MASTER is a joint NCT program between NCT Heidelberg and NCT/UCC Dresden. You can find more information about registering for the program here or download the flyer here.

Center for Personalized Oncology

The NCT/UCC Dresden Center for Personalized Oncology aims at translating latest research as well as innovative technologies and cancer therapies into clinical practice. A dedicated personalized oncology outpatient clinic provides consulting appointments to discuss innovative diagnostic approaches, results of genetic tumor profiling and molecularly guided treatment strategies. Clinical data and results of molecular analyses as well as potential therapeutic implications are discussed within a molecular tumor board participated by an interdisciplinary team of specialists in molecular diagnostics, targeted cancer therapy as well as involved clinical departments.

Dr. Christoph Heining
Senior Attending Physician
Email: christoph.heining(at)nct-dresden.de

Non-coding RNAs (ncRNAs) are functional RNA molecules that are transcribed from DNA but not translated into proteins. Considering that only around 2% of the human transcriptome is translated, ncRNAs represent a huge proportion of the DNA encoded genetic information. Many ncRNA subspecies have been described, for instance microRNAs, small nucleolar RNAs or long non-coding RNAs (lncRNAs). They play pivotal roles in a plethora of cellular processes in development and diseases, including cancer, and can interact with nearly all cellular components.
By exploring various cancer entities and state-of-the art techniques, we want to demonstrate that non-coding RNAs can drive tumorigenesis and influence anti-cancer treatment response. In addition, we will explore their suitability to function as biomarkers for precision oncology based approaches.

RESEARCH AIMS

  • Identification and characterization of cancer-driving ncRNAs
  • Characterization of ncRNA-epigenome landscapes in various cancers
  • Defining prognostic ncRNA scores for different targeted cancer therapies
  • Exploring therapy resistance associated ncRNAs

Dr. Alexander Wurm
Group Leader
Email: alexander.wurm(at)nct-dresden.de

Dr. Marius Bill
Attending Physician
Email: marius.bill(at)nct-dresden.de

MSNZ fellowship: Non-coding RNAs in cancer

The department closely collaborates with the Mildred-Scheel-Group “Biomedical Genomics”, headed by Dr. Anna Poetsch, exploring the possibilities of novel functional genomics and machine learning approaches to investigate DNA-damage response mechanisms in cancer.

Dr. Anna Poetsch
Group Leader
Email: anna.poetsch(at)tu-dresden.de

MSNZ fellowship: Biomedical Genomics

Contact

Prof. Dr. Hanno Glimm
Head of Department
Translational Medical Oncology
Phone: +49 (0)351 458 5531
E-Mail: hanno.glimm(at)nct-dresden.de

Yasmin Führer
Secretary
Phone: +49 (0)351 458 5531
E-Mail: yasmin.fuehrer(at)nct-dresden.de​​​​​​​​​​​​​​

Dr. Daniela Richter
Scientific and Administrative Coordinator
Phone: +49 (0)351 458 5539
E-Mail: daniela.richter(at)nct-dresden.de

Head of Department

  • Prof. Dr. med. Hanno Glimm, head of department, specialist for internal medicine, hematology and oncology, hanno.glimm(at)nct-dresden.de, +49 (0)351 458 5540

Administration

Experimental Translational Oncology

Clinical Translational Oncology

Non-coding RNAs in Leukemia

Biomedical Genomics

Alumni

 

2021

Horak P, Leichsenring J, Goldschmid H, et al. Assigning evidence to actionability: an introduction to variant interpretation in precision cancer medicine. Genes Chromosomes Cancer. Published online July 30, 2021. doi:10.1002/gcc.22987

Horak P, Heining C, Kreutzfeldt S, et al. Comprehensive Genomic and Transcriptomic Analysis for Guiding Therapeutic Decisions in Patients with Rare Cancers. Cancer Discov. Published online June 10, 2021. doi:10.1158/2159-8290.CD-21-0126

Simon M, Mughal SS, Horak P, et al. Deconvolution of sarcoma methylomes reveals varying degrees of immune cell infiltrates with association to genomic aberrations. J Transl Med. 2021;19(1):204. doi:10.1186/s12967-021-02858-7

Hübschmann D, Jopp-Saile L, Andresen C, et al. Analysis of mutational signatures with yet another package for signature analysis. Genes Chromosomes Cancer. 2021;60(5):314-331. doi:10.1002/gcc.22918

Uhrig S, Ellermann J, Walther T, et al. Accurate and efficient detection of gene fusions from RNA sequencing data. Genome Res. 2021;31(3):448-460. doi:10.1101/gr.257246.119

Hanf D, Heining C, Laaber K, et al. Response to Cabozantinib Following Acquired Entrectinib Resistance in a Patient With ETV6-NTRK3 Fusion-Positive Carcinoma Harboring the NTRK3 G623R Solvent-Front Mutation. JCO Precis Oncol. 2021;5:PO.20.00278. doi:10.1200/PO.20.00278

2020

Mc Connell L, Gazdova J, Beck K, et al. Detection of Structural Variants in Circulating Cell-Free DNA from Sarcoma Patients Using Next Generation Sequencing. Cancers (Basel). 2020;12(12). doi:10.3390/cancers12123627

Loosen SH, Gaisa NT, Schmeding M, et al. Prolonged Survival of a Patient with Advanced-Stage Combined Hepatocellular-Cholangiocarcinoma. Case Rep Gastroenterol. 2020;14(3):658-667. doi:10.1159/000511034

Scherr A-L, 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(10):875. doi:10.1038/s41419-020-03092-7

Messerschmidt C, Obermayer B, Klinghammer K, et al. Distinct immune evasion in APOBEC-enriched, HPV-negative HNSCC. Int J Cancer. 2020;147(8):2293-2302. doi:10.1002/ijc.33123

Heilig CE, Horak P, Lipka DB, et al. Germline SDHB-inactivating mutation in gastric spindle cell sarcoma. Genes Chromosomes Cancer. 2020;59(10):601-608. doi:10.1002/gcc.22876

Wahjudi LW, Bernhardt S, Abnaof K, et al. Integrating proteomics into precision oncology. Int J Cancer. Published online September 19, 2020. doi:10.1002/ijc.33301

Munkhbaatar E, Dietzen M, Agrawal D, et al. MCL-1 gains occur with high frequency in lung adenocarcinoma and can be targeted therapeutically. Nat Commun. 2020;11(1):4527. doi:10.1038/s41467-020-18372-1

Rippinger N, Fischer C, Haun MW, et al. Cancer surveillance and distress among adult pathogenic TP53 germline variant carriers in Germany: A multicenter feasibility and acceptance survey. Cancer. 2020;126(17):4032-4041. doi:10.1002/cncr.33004

Westphalen BC, Bokemeyer C, Büttner R, et al. Conceptual framework for precision cancer medicine in Germany: Consensus statement of the Deutsche Krebshilfe working group “Molecular Diagnostics and Therapy.” Eur J Cancer. 2020;135:1-7. doi:10.1016/j.ejca.2020.04.019

Busch E, Kreutzfeldt S, Agaimy A, et al. Successful BRAF/MEK inhibition in a patient with BRAFV600E-mutated extrapancreatic acinar cell carcinoma. Cold Spring Harb Mol Case Stud. 2020;6(4). doi:10.1101/mcs.a005553

Tamborero D, Dienstmann R, Rachid MH, et al. Support systems to guide clinical decision-making in precision oncology: The Cancer Core Europe Molecular Tumor Board Portal. Nat Med. 2020;26(7):992-994. doi:10.1038/s41591-020-0969-2

Roider T, Seufert J, Uvarovskii A, et al. Dissecting intratumour heterogeneity of nodal B-cell lymphomas at the transcriptional, genetic and drug-response levels. Nat Cell Biol. 2020;22(7):896-906. doi:10.1038/s41556-020-0532-x

Kommoss FK, Chang KT, Stichel D, et al. Endometrial stromal sarcomas with BCOR-rearrangement harbor MDM2 amplifications. J Pathol Clin Res. 2020;6(3):178-184. doi:10.1002/cjp2.165

Ronellenfitsch MW, Harter PN, Kirchner M, et al. Targetable ERBB2 mutations identified in neurofibroma/schwannoma hybrid nerve sheath tumors. J Clin Invest. 2020;130(5):2488-2495. doi:10.1172/JCI130787

Berger AK, Mughal SS, Allgäuer M, et al. Metastatic adult pancreatoblastoma: Multimodal treatment and molecular characterization of a very rare disease. Pancreatology. 2020;20(3):425-432. doi:10.1016/j.pan.2020.02.017

Brown AL, Arts P, Carmichael CL, et al. RUNX1-mutated families show phenotype heterogeneity and a somatic mutation profile unique to germline predisposed AML. Blood Adv. 2020;4(6):1131-1144. doi:10.1182/bloodadvances.2019000901

Stenzinger A, Endris V, Budczies J, et al. Harmonization and Standardization of Panel-Based Tumor Mutational Burden (TMB) Measurement: Real-World Results and Recommendations of the QuIP Study. J Thorac Oncol. Published online February 28, 2020. doi:10.1016/j.jtho.2020.01.023

Mogler C, Koschny R, Heilig CE, et al. Molecular characterization of hepatic epithelioid hemangioendothelioma reveals alterations in various genes involved in DNA repair, epigenetic regulation, signaling pathways, and cell cycle control. Genes Chromosomes Cancer. 2020;59(2):106-110. doi:10.1002/gcc.22795

Weinberg F, Griffin R, Fröhlich M, et al. Identification and characterization of a BRAF fusion oncoprotein with retained autoinhibitory domains. Oncogene. 2020;39(4):814-832. doi:10.1038/s41388-019-1021-1

Voronina N, Wong JKL, Hübschmann D, et al. The landscape of chromothripsis across adult cancer types. Nat Commun. 2020;11(1):2320. doi:10.1038/s41467-020-16134-7

Schickhardt C, Horak P, Fröhling S, Winkler EC. The molecular tumor board. Ethical challenges and recommendations for practice. Onkologe 26:431-437, 2020.

Mock A, Heilig CE, Kreutzfeldt S, et al. Molecular characterization of hepatic epithelioid hemangioendothelioma reveals alterations in various genes involved in DNA repair, epigenetic regulation, signaling pathways and cell cycle control. Genes Chromosomes Cancer 59:106-110, 2020.

2019

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.

Mühlenberg T, Ketzer J, Heinrich MC, et al. KIT-dependent and -independent genomic heterogeneity of resistance in gastrointestinal stromal tumors: TORC1/2 inhibition as salvage strategy. Mol Cancer Ther 18:1985-1996, 2019.

Gröschel S, Hübschmann D, Raimondi F, et al. Defective homologous recombination DNA repair as therapeutic target in advanced chordoma. Nat Commun 10:1635, 2019.

Horak P, Weischenfeldt J, von Amsberg G, et al. Response to olaparib in a PALB2 germline mutated prostate cancer and genetic events associated with resistance. Cold Spring Harb Mol Case Stud 5:a003657, 2019.

Leichsenring J, Horak P, Kreutzfeldt S, et al. Variant classification in precision oncology. Int J Cancer 145:2996-3010, 2019.

2018

Lier A, Penzel R, Heining C, et al. Validating comprehensive next-generation sequencing results for precision oncology: the NCT/DKTK MASTER experience. JCO Precis Oncol 2:1-13, 2018.

Heining C, Horak P, Uhrig S, et al. NRG1 fusions in KRAS wild-type pancreatic cancer. Cancer Discov 8:1087-1095, 2018.

Terziev D, Hutter B, Klink B, et al. Nivolumab maintenance after salvage autologous stem cell transplantation results in long-term remission in multiple relapsed primary CNS lymphoma. Eur J Haematol 101:115-118, 2018.

Perera-Bel J, Hutter B, Heining C, et al. From somatic variants towards precision oncology: evidence-driven reporting of treatment options in molecular tumor boards. Genome Med 10:18, 2018.

Chudasama P, Mughal SS, Sanders MA, et al. Integrative genomic and transcriptomic analysis of leiomyosarcoma. Nat Commun 9:144, 2018.

2017

Forschner A, Niessner H, Möller Y, et al. Genomics of immunotherapy-associated hyperprogressors. Clin Cancer Res 23:6374-6375, 2017.

Ugurel S, Kiecker F, Fröhling S, et al. Fulminant response to combined checkpoint inhibition with ipilimumab plus nivolumab after failure of nivolumab monotherapy in metastatic melanoma. Eur J Cancer 83:142-145, 2017.

Czink E, Kloor M, Goeppert B, et al. Successful immune checkpoint blockade in a patient with advanced stage microsatellite unstable biliary tract cancer. Cold Spring Harb Mol Case Stud 3:a001974, 2017.

Gröschel S, Bommer M, Hutter B, et al. Integration of genomics and histology reveals diagnosis and effective therapy of refractory cancer of unknown primary with PDL1 amplification. Cold Spring Harb Mol Case Stud 2:a001180, 2016.

Dieter SM, Heining C, Agaimy A, et al. Mutant KIT as imatinib-sensitive target in metastatic sinonasal carcinoma. Ann Oncol 28:142-148, 2017.

Bochtler T, Fröhling S, Weichert W, et al. Evolution of a FLT3-TKD mutated subclone at meningeal relapse in acute promyelocytic leukemia. Cold Spring Harb Mol Case Stud 2:a001123, 2016.

Chudasama P, Renner M, Straub M, et al. Targeting FGFR1 for treatment of soft-tissue sarcoma. Clin Cancer Res 23:962-973, 2017.

Heining C, Horak P, Gröschel S, Glimm H, Fröhling S. Personalized oncology. Radiologe 57:804-811, 2017.

Horak P, Klink B, Heining C, et al. Precision oncology based on omics data: the NCT Heidelberg experience. Int J Cancer 141:877-886, 2017.

2016

Czink E, Heining C, Weber TF, et al. Durable remission under dual HER2 blockade with trastuzumab and pertuzumab in a patient with metastatic gallbladder cancer. Z Gastroenterol 54:426-430, 2016.

Kordes M, Röring M, Heining C, et al. Cooperation of BRAF F595L and mutant HRAS in histiocytic sarcoma provides new insights into oncogenic BRAF signaling. Leukemia 30:937-946, 2016.

Horak P, Fröhling S, Glimm H. Integrating next-generation sequencing into clinical oncology: strategies, promises and pitfalls. ESMO Open 1:e000094, 2016.

2015

Dietrich S, Hüllein J, Lee SC, et al. Recurrent CDKN1B (p27) mutations in hairy cell leukemia. Blood 126:1005-1008, 2015.

Husedzinovic A, Ose D, Schickhardt C, Fröhling S, Winkler EC. Stakeholders’ perspectives on biobank-based genomic research: systematic review of the literature. Eur J Hum Genet 23:1607-1614, 2015.

2014

Yaktapour N, Meiss F, Mastroianni J, et al. BRAF inhibitor-associated ERK activation drives development of chronic lymphocytic leukemia. J Clin Invest 124:5074-5084, 2014.

2013

Dietrich S, Hüllein J, Hundemer M, et al. Continued response off treatment after BRAF inhibition in refractory hairy cell leukemia. J Clin Oncol 31:e300-3, 2013.

Open Positions

For the upcoming winter semester 2021/22 we offer bachelor/master thesis and lab rotations positions for life sciences students. Interested students are welcome to submit an application including motivation letter and certificates by 31st July 2021 to julia.dorok(at)nct-dresden.de