Department for Translational Medical Oncology

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.

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 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.

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 personalized oncology tumorboard participated by an interdisciplinary team of specialists in molecular diagnostics, targeted cancer therapy as well as involved clinical departments.

Tirier, S. M.; Park, J.; Preußer, F; et al. Pheno-Seq - Linking Visual Features and Gene Expression in 3D Cell Culture Systems. Sci Rep 2019, 9 (1), 12367. https://doi.org/10.1038/s41598-019-48771-4.

Gröschel, S.; Hübschmann, D.; Raimondi, F.; et al. Defective Homologous Recombination DNA Repair as Therapeutic Target in Advanced Chordoma. Nat Commun 2019, 10 (1), 1635. https://doi.org/10.1038/s41467-019-09633-9.

Wünsche, P.; Eckert, E. S. P.; Holland-Letz, T.; et al. Mapping Active Gene-Regulatory Regions in Human Repopulating Long-Term HSCs. Cell Stem Cell 2018, 23 (1), 132-146.e9. https://doi.org/10.1016/j.stem.2018.06.003.

Heining, C.; Horak, P.; Uhrig, S.; et al. NRG1 Fusions in KRAS Wild-Type Pancreatic Cancer. Cancer Discov 2018, 8 (9), 1087–1095. https://doi.org/10.1158/2159-8290.CD-18-0036.

Bormann, F.; Rodríguez-Paredes, M.; Lasitschka, F.; et al. Cell-of-Origin DNA Methylation Signatures Are Maintained during Colorectal Carcinogenesis. Cell Rep 2018, 23 (11), 3407–3418. https://doi.org/10.1016/j.celrep.2018.05.045.

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 2018, 10 (1), 18. https://doi.org/10.1186/s13073-018-0529-2.

Giessler, K. M.; Kleinheinz, K.; Huebschmann, D.; et al. Genetic Subclone Architecture of Tumor Clone-Initiating Cells in Colorectal Cancer. J. Exp. Med. 2017, 214 (7), 2073–2088. https://doi.org/10.1084/jem.20162017.

Dieter, S. M.; Glimm, H.; Ball, C. R. Colorectal Cancer-Initiating Cells Caught in the Act. EMBO Mol. Med. 2017, 9 (7), 856–858. https://doi.org/10.15252/emmm.201707858.

Horak, P.; Klink, B.; Heining, C.; et al. Precision Oncology Based on Omics Data: The NCT Heidelberg Experience. Int. J. Cancer 2017, 141 (5), 877–886. https://doi.org/10.1002/ijc.30828.

Ball, C. R.; Oppel, F.; Ehrenberg, K. R.; et al. Succession of Transiently Active Tumor-Initiating Cell Clones in Human Pancreatic Cancer Xenografts. EMBO Mol Med 2017, 9 (7), 918–932. https://doi.org/10.15252/emmm.201607354.

Dieter, S. M.; Giessler, K. M.; Kriegsmann, M.; et al. Patient-Derived Xenografts of Gastrointestinal Cancers Are Susceptible to Rapid and Delayed B-Lymphoproliferation. Int. J. Cancer 2017, 140 (6), 1356–1363. https://doi.org/10.1002/ijc.30561.

Weischenfeldt, J.; Dubash, T.; Drainas, A. P.; et al. Pan-Cancer Analysis of Somatic Copy-Number Alterations Implicates IRS4 and IGF2 in Enhancer Hijacking. Nat. Genet. 2017, 49 (1), 65–74. https://doi.org/10.1038/ng.3722.

Dubash, T. D.; Hoffmann, C. M.; Oppel, F.; et al. Phenotypic Differentiation Does Not Affect Tumorigenicity of Primary Human Colon Cancer Initiating Cells. Cancer Lett. 2016, 371 (2), 326–333. https://doi.org/10.1016/j.canlet.2015.11.037.

Horak, P.; Fröhling, S.; Glimm, H. Integrating Next-Generation Sequencing into Clinical Oncology: Strategies, Promises and Pitfalls. ESMO Open 2016, 1 (5), e000094. https://doi.org/10.1136/esmoopen-2016-000094.