Project Details
Projekt
Targeting the Ferroptosis regulatory network in multiple myeloma and hematological malignancies
Subject Area
Hematology, Oncology
Term
since 2021
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 456200217
Multiple myeloma (MM) is a still largely incurable B cell disease caused by accumulation and expansion of malignant plasma cells mainly in but not restricted to bone marrow. Current standard treatment is based on a number of combination approaches including chemotherapeutic agents, corticosteroids, proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies against CD38 and CD319. However, most patients develop drug resistance during the course of therapy and eventually succumb to the disease. Therefore, evaluation of novel therapeutic approaches remains a challenging task. We hypothesize that targeting of ferroptosis, a recently discovered cell death modality, might represent such a novel treatment strategy, because it has been shown to induce cell death in chemotherapy-refractory cancer cells. Own preliminary data revealed expression of the newly identified ferroptosis regulator Ferroptosis Suppressor Protein 1 (FSP1) in human MM cell lines and in primary cells from MM patients. In addition, we observed that overexpression of FSP1 in MM cell lines supports cell growth under a range of metabolically relevant stress conditions. In order to characterize ferroptosis and FSP1 as a potential therapeutic target in MM, we aim to achieve the following objectives in our application: i) characterization of ferroptosis regulation in MM, in particular in regards to sensitivity towards ferroptosis-mediated cell death, ii) the role and transcriptional regulation of FSP1, and iii) the role of FSP1 for the growth of MM cells under therapy-induced and metabolic stress conditions in MM mouse models.
DFG Programme
Research Grants
