IDENTIFICATION AND VALIDATION OF NOVEL DRUG TARGETS FOR TREATMENT OF MULTIPLE MYELOMA
Despite the impressive therapeutic progress achieved in myeloma over the last decades, resulting in a 7–10-year average survival, the vast majority of patients are not cured. To advance towards a personalised treatment strategy with the ultimate aim of cure, significant efforts are required to identify therapeutic vulnerabilities in myeloma and to advance these into therapeutic modalities. This requires an alliance between medicinal chemists, basic scientists, clinicians and pharmacologists across academia, biotech and pharmaceutical industry. We are collaborating with multiple national and international organisations and institutions to investigate, identify and validate possible novel therapeutic approaches in myeloma.
UNDERSTANDING THE BONE AND IMMUNE MICROENVIRONMENT IN MYELOMA
The myeloma tumour primarily resides in the bone marrow, an anatomical compartment that is essential for many physiological functions. The bone marrow harbours a complex microenvironment consisting of mesenchymal stromal cells, fibroblasts, adipocytes, endothelial cells, osteoclasts, osteoblasts, immune cells and hematopoietic cells. Cells are embedded in a non-cellular compartment of the extracellular matrix and surrounded by cytokines, growth factors, chemokines and extracellular vesicles.
The bone marrow microenvironment plays a pivotal role in mediating survival, proliferation, drug resistance, and progression of the disease. In order to better understand myeloma pathology and identify possible therapeutic approaches we are studying the complex interactions between myeloma and its microenvironment using a variety of state of the art technologies, including next-generation sequencing (single-cell transcriptomics, genomics), imaging (multiplexed immune fluorescence, imaging mass cytometry), flow and mass cytometry, as well as mass spectrometry based proteomics and metabolomics.