Current treatment strategies against multiple myeloma are based on a combination of proteasome inhibitors, immune modulatory drugs, and monoclonal antibodies, as well as chemotherapy with autologous stem cell transplantation. Despite improved survival rates, long term remission or even cure is still rarely achieved. Personalizing tumor specific therapy is currently explored to improve the outcome of specific patient groups by correlating genomic, proteomic and clinical data of refractory myeloma patients.
In order to understand mechanisms underlying drug resistance in multiple myeloma, we compare the evolution of the clonal structure of tumor cells along treatment in clinical trials and routine care with the aim to discover novel therapeutic targets in refractory disease. By combining NGS-based readouts (WGS, RNAseq, scRNAseq, scATACseq, CiteSeq) with proteome-based technologies we comprehensively map cellular signaling profiles in order to identify biomarkers as well as novel therapeutic targets. We further focus on tumor heterogeneity within individual multiple myeloma patients to understand the full spectrum of disease biology and specifically the role of residual tumor cells in clinical remission.
Overall, our goal is to understand the complex processes underlying the heterogeneity of this disease. We aim to discover molecular mechanisms that lead to drug resistance, impairment of the immune microenvironment, and result in novel therapeutic targets. Due to our strong clinical affiliation with the University Hospital, we successfully translate our discoveries in clinical application.