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SFB 1530:  Elucidation and targeting of pathogenic mechanisms in B cell malignancies

Subject Area Medicine
Biology
Term since 2022
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Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 455784452
 
Despite considerable progress during the last decades, lymphoid malignancies continue to represent a major health problem. Today, B cell malignancies represent 4% of all cancers, and the 10-year relative overall survival in Germany is at 55-70%. Resistance to induction therapy or disease progression represent major clinical problems. The majority of patients suffering from relapsed and/or refractory lymphoma eventually succumb to their disease. Overall, B cell malignancies account for 3% of all cancer-related deaths, holding the 6th position of all cancers. The overall goal of this consortium is to significantly increase the cure rate of high-risk B cell malignancies over the next 12 years by providing a molecular framework for innovative mechanism-based therapies. The main scientific focus will lie on mechanisms of treatment failure and the development of improved therapies. It follows our vision that improved patient outcomes can be achieved through the synergistic combination of an efficient disruption of lymphoma cell-intrinsic oncogenic programs and a specific modulation of the lymphoma (immune) microenvironment. To this end, this consortium will create mechanistic insights and discoveries in essential aspects of lymphoma biology. These areas are 1) the elucidation of actionable B cell-specific oncogenic signaling pathways; 2) the characterization of druggable interactions within the lymphoma microenvironment; and 3) the creation of a mechanistic understanding of the (epi-)genetic and proteomic heterogeneity of lymphomas and their spatio-temporal evolution under different conditions, including therapeutic stress. To reach these goals, the consortium will follow a three-pronged approach: 1. Conducting mechanistic studies in lymphoma models to understand the tumor cell autonomous and non-cell autonomous mechanisms driving lymphomagenesis and disease progression. 2) Leveraging these mechanistic insights to identify specific targetable vulnerabilities. 3) Performing longitudinal investigation of (epi)genetic and proteomic alterations in bulk analyses, at a single cell level or in large, well-characterized lymphoma patient cohorts to gain a comprehensive understanding of the clonal lymphoma evolution. The consortium will integrate the strengths of a group of excellent scientists with highly complementary skills, technical know-how and expertise. Importantly, the cooperation of investigators with track-records in either lymphoma or inflammation research will create synergies towards the discovery of pathomechanisms and the identification of novel therapeutic strategies. In summary, the consortium will undertake a holistic and interdisciplinary effort, which will create a comprehensive inventory of the major pathomechanisms that define high-risk B cell malignancies in their specific microenvironment as a molecular framework for mechanism-based therapies.
DFG Programme Collaborative Research Centres

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Applicant Institution Universität zu Köln
Participating Institution Deutsches Krebsforschungszentrum (DKFZ)
 
 

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