Project Details
Projekt
Selenium metabolism and its contribution to ferroptosis resistance
Subject Area
Cell Biology
Term
since 2021
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 461445936
Ferroptosis, a regulated cell death process, offers a promising strategy for targeting cancer cells dependent on the selenoprotein GPX4. Despite considerable interest, the lack of specific GPX4 inhibitors effective in vivo poses a challenge in translating ferroptosis-based therapies to clinical use. Our proposed approach addresses this challenge by targeting selenocysteine metabolism, a rare amino acid crucial for GPX4 function. In our initial funding period, we demonstrated the potential benefits of targeting this pathway in MYCN-amplified neuroblastoma models. Our strategy involves a combination of cellular and biochemical methods to thoroughly understand selenocysteine mobilization mechanisms in cells. Additionally, through structural characterization of key pathway components, we aim to gain molecular insights into selenium utilization and identify novel small molecules targeting this pathway. These efforts will advance our understanding of ferroptosis induction mechanisms and facilitate the development of new therapeutic approaches. This research has the potential to translate ferroptosis-based therapies into clinical applications, offering effective treatment options for cancer patients.
DFG Programme
Priority Programmes
