Max-Eder-Junior Research Group Experimental therapies for hematologic malignancies
Dr. med. Marc S. Raab
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
Raab MS, Podar K, Breitkreutz I, Richardson PG, Anderson KC (2009). Multiple Myeloma. Lancet, 374(9686):324-39
Raab MS, Breitkreutz I, Tonon G, Zhang J, Hayden PJ, Nguyen T et al. (2009). Targeting PKC: A novel role for beta-catenin in ER stress and apoptotic signaling. Blood., 113(7):1513-21.
Krämer A, Raab MS, Rebacz B. (2008). Induction of spindle multipolarity by centrosomal cluster inhibition. Cell Oncol, 30(6):505
Raab MS, Breitkreutz I, Anderson KC. (2007) Targeted treatments to improve stem cell outcome: old and new drugs. Bone Marrow Transplant, 40(12):1129-37.