Periodic Reporting for period 1 - MetaIron (Targeting Mfrn2 to Inhibit Metastatic Cancers)
Reporting period: 2023-06-01 to 2024-11-30
The majority of cancer patients dies due to metastasis formation in distant organs. To date, we unfortunately largely lack effective therapies for preventing or treating an already developed metastatic disease. The effect of this lack of treatment options against metastatic cancers is dramatically illustrated for breast cancer. At early-stage disease the 5-year survival rate for breast cancer patients is more than 90%, however, once metastases arise this drops to less than 20%, resulting in over 685,000 deaths per year. Thus, there is an urgent need to develop novel therapeutic options that can prevent or treat metastases in multiple organs. We evaluated targeting iron metabolism to inhibit metastasis growth.
We investigated Mfrn2 (SLC25A28) as a drug target against metastases. Mfrn2 is a mitochondrial iron transporter. A patent application for the use of Mfrn2 as a drug target was filed (EP 21216949.4.). Assays to screen for Mfrn2 inhibitors were researched. In collaboration with the EU funded RESOLUTE consortium drug screens were performed and candidates ranked. Further mouse experiments were performed. The relation of iron levels to distant metastasis was evaluated in a cohort of patients (manuscript in revision). Overall, we concluded that iron metabolism is an important drug target but that the nature of Mfrn2 as solute carrier remains challenging to develop isoform selective therapies.
We established collaborations and interactions with the EU funded consortium RESOLUTE.