Experimental therapies for hematologic malignancies

Max-Eder-Junior Research Group Experimental therapies for hematologic malignancies

Dr. med. Marc S. Raab

Multipolar Mitosis of a mouse xenograft under treatment with a prototype inhibitor of centrosomal clustering.
© dkfz.de

Despite recent advances, most cancers of the blood and bone marrow remain incurable.
Our group is therefore focused on understanding critical pathophysiological mechanisms of hematologic malignancies to enable the identification of innovative therapeutic targets and treatment strategies.
Together with the Clinical Cooperation Unit Molecular Hematology/Oncology (G330, Prof. A. Krämer), we are currently investigating the clustering of supernumerary centrosomes. This is a well-recognized cellular process on which cancer cell growth is dependent. We are therefore working to decipher the mechanism of centrosomal clustering in hematologic malignancies with a view to the development of specific inhibitors to exploit this mechanism for therapeutic ends.
In our model disease, multiple myeloma, we aim to discover molecular mechanisms of the pivotal transition from its premalignant precursor state to the active malignant stage. Here, we are focusing on the regulation of the cell cycle that seems to prevent clonal growth of premalignant stages compared to active myeloma.
We are also interested in the evaluation of novel agents which inhibit cellular pathways known to be important in myeloma pathogenesis. This work is done in collaboration with our industry partners who provide promising compounds for assessment in our extensive pre-clinical models. We also participate in several national and international clinical trials including First-in-Man applications as well as first-in-class studies.

All our projects are aimed at the discovery of new therapeutic targets, investigating new treatment strategies, and ultimately improve patient outcome.

Our group has 3 major goals:

Develop novel therapeutic approaches based on centrosomal clustering
To further develop our first prototype inhibitors of centrosomal clustering preclinically and to establish a robust and specific high throughput small molecule screen

Discover key events in myeloma pathogenesis
To investigate the pivotal transition from the pre-malignant, asymptomatic to malignant, symptomatic stages of plasma cell dyscrasias in order to understand the pathophysiology and thereby identify novel targets

Translate small molecule therapeutics from bench to clinical trials
To evaluate novel agents in the preclinical setting and to initiate early phase clinical trials in hematologic malignancies with focus on multiple myeloma

Contact

Dr. med. Marc S. Raab
Experimental therapies for hematologic malignancies (G170)
Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 280
69120 Heidelberg
Tel: +49 6221 42 1450

Selected Publications

  • Raab M.S. et al (2016). Spatially divergent clonal evolution in multiple myeloma: overcoming resistance to BRAF inhibition. Blood, 127(17), 2155-2157.
  • Andrulis M, Lehners N, Capper D, Penzel R, Heining C, Huellein J, Zenz T, von Deimling A, Schirmacher P, Ho AD, Goldschmidt H, Neben K, Raab MS. (2013) Targeting the BRAF V600E mutation in multiple myeloma. Cancer Discov. 3(8):862-9.
  • Raab MS, Breitkreutz I, Anderhub S, Rønnest MH, Leber B, Larsen TO, Weiz L, Konotop G, Hayden PJ, Podar K, Fruehauf J, Nissen F, Mier W, Haberkorn U, Ho AD, Goldschmidt H, Anderson KC, Clausen MH, Krämer A. (2012) GF-15, a novel inhibitor of centrosomal clustering, suppresses tumor cell growth in vitro and in vivo. Cancer Res. 72(20):5374-85.
  • Raab MS, Podar K, Breitkreutz I, Richardson PG, Anderson KC. (2009) Multiple myeloma. Lancet 25;374(9686):324-39.
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