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Clinical Cooperation Unit Molecular Hematology/Oncology

Prof. Dr. Alwin Krämer

© dkfz.de

The Clinical Cooperation Unit Molecular Hematology/Oncology has a translational/clinical research focus on cancer of unknown primary (CUP), while its basic science centers around causes and consequences of chromosomal instability (CIN), and its impact on metastatic seeding.

Cancer of unknown primary (CUP) is a paradigm metastatic malignancy, in which only metastases but no primary tumor can be identified. To improve on its dismal prognosis, we have initiated large clinical trials, examining the benefits of mutation-based targeted treatments and immunotherapy compared to standard chemotherapy. Within the frame of these clinical trials, our translational research program explores the mechanisms responsible for early and aggressive metastatic seeding in CUP syndrome. For that, tumor, serum, germline and liquid biopsy/ctDNA samples of patients as well as patient-derived organoids (PDO) are examined using multi-omics technologies as well as in-vitro and in-vivo model systems. Additionally, individual PDO cultures are used for in-vitro drug screening to predict the efficacy of conventional chemotherapy, targeted compounds and immune-checkpoint inhibitors. Overarching goals are the development of novel treatment options for patients with metastatic cancers and, ultimately, the prevention of metastatic spread as the major cause of death from almost all types of malignancies.

Chromosomal instability (CIN) is a nearly universal feature of human malignancies and a major contributor to genetic heterogeneity, clonal evolution and metastasis, themselves being at the center of cancer development, progression and treatment resistance. Within the frame of our translational/clinical research efforts, our basic research therefore explores the contribution of chromosomal instability to the metastatic process and the poor prognosis of patients with CUP and other metastatic malignancies.

The Translational Myeloma Research Group of the Heidelberg Myeloma Center focuses on molecular and pathophysiologic aspects of multiple myeloma, with special interest in mechanisms of drug resistance, spatial heterogeneity of clonal evolution, and novel therapeutic targets. Our group serves as the translational research core of the German-speaking Multiple Myeloma Study Group (GMMG) and is responsible for many correlative science projects in the context of multicenter clinical trials.

Contact

Prof. Dr. Alwin Krämer
Molecular Hematology/Oncology (A360)
Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 280
69120 Heidelberg

Tel: +49-6221-42-1440 (DKFZ)
+49-6221-56-38183 (Klinik)
E-Mail: a.kraemer@dkfz.de (DKFZ)
Alwin_Kraemer@med.uni-heidelberg.de (Klinik)

Selected Publications

  • 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. Nature Communications 14(1): 6761, 2023.
  • Köhrer S, Dittrich T, Schorb M, Weinhold N, Haberbosch I, Börmel M, Pajor G, Goldschmidt H, Müller-Tidow C, Raab MS, John L, Seckinger A, Brobeil A, Dreger P, Tornóczky T, Pajor L, Hegenbart U, Schönland SO, Schwab Y, Krämer A: High-throughput electron tomography identifies centriole over-elongation as an early event in plasma cell disorders. Leukemia (Online ahead of print), 2023.
  • Krämer A, Bochtler T, Pauli C, Baciarello G, Delorme S, Hemminki K, Mileshkin L, Moch H, Oien K, Olivier T, Patrikidou A, Wasan H, Zarkavelis G, Pentheroudakis G, Fizazi K, on behalf of the ESMO Guidelines Committee: Cancer of unknown primary: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Annals of Oncology. 34: 228-246, 2023.
  • Pouyiourou M, Wohlfromm T, Kraft B, Hielscher T, Stichel D, von Deimling A, Delorme S, Endris V, Neumann O, Stenzinger A, Krämer A, Bochtler T: Local ablative treatment with surgery and/or radiotherapy in single-site and oligometastatic carcinoma of unknown primary (CUP). European Journal of Cancer 157: 179-189, 2021.
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