Collaborative Research Center 1530:
Elucidation and targeting of pathogenic mechanisms in B cell malignancies
Modern-day therapy to treat lymphoid malignancies is witnessing a paradigmatic shift. During the last decades considerable progress has been made away from globally toxic chemo- and radiotherapy, towards the use of non-genotoxic targeted small molecules and antibodies. These efforts are rooted in a steadily deepening molecular understanding of the patho-mechanisms underlying malignant transformation.
However lymphoid malignancies remain a major health problem and resistance to induction therapy or disease progression are important clinical challenges. As the majority of patients suffering from relapsed and/or refractory lymphoma eventually succumb to their disease, B cell malignancies account for 3% of all cancer-related deaths.
The declared goal of CRC 1530 is to significantly increase therapeutic responses and cure rates of high-risk B cell malignancies over the next decade by providing a molecular framework for innovative, mechanism-based therapies. The main scientific focus will be placed on elucidating the molecular mechanisms of response and resistance to treatment, as well as the development of advanced diagnostic and therapeutic algorithms.
To achieve these goals, we will follow a three-pronged approach: 1) Conducting mechanistic studies in lymphoma models to understand the tumour cell autonomous and non-autonomous mechanisms driving lymphoma development, progression and drug resistance. 2) Leveraging these mechanistic insights to identify specific actionable vulnerabilities. 3) Performing longitudinal investigation of (epi-) genetic and alterations in bulk analyses, at a single cell level or in large, well-characterized lymphoma patient cohorts to gain a comprehensive understanding of lymphoma biology, heterogeneity and response to therapy.
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