Innovative Approach Using Iron to Target Multiple Myeloma Cells
Duke University researchers have discovered that inhibiting the enzyme STK17B can trigger ferroptosis in multiple myeloma cells, offering a new promising treatment strategy to overcome drug resistance and improve outcomes for patients.
Researchers at Duke University have uncovered a promising new strategy to combat multiple myeloma (MM), an incurable blood cancer affecting plasma cells. Their study reveals that inhibiting a specific enzyme involved in iron regulation can not only eliminate MM cancer cells but also enhances the effectiveness of existing treatments. Published on September 12 in the journal Blood, this research highlights the potential of targeting iron-related pathways to fight this disease.
Multiple myeloma originates in plasma cells within the bone marrow, where abnormal cell buildup disrupts normal blood cell production, weakens the immune system, damages organs like the kidneys, and causes painful bone lesions. Despite advancements with targeted therapies, relapse and drug resistance remain significant hurdles.
A key insight from the study is that MM cells often suppress ferroptosis, a natural form of cell death triggered by excess iron accumulation. Normally, ferroptosis damages cell membranes and leads to cell destruction, but cancer cells evade this process to survive despite high iron levels. Lead researcher Mikhail Nikiforov explains that MM cells adapt to resist iron-induced cell death, thanks to mechanisms largely unknown until now.
The Duke team identified the enzyme STK17B as a crucial regulator in this resistance pathway. Elevated levels of STK17B correlate with poorer outcomes and are especially high in relapsed cases. By inhibiting STK17B with a specially developed compound, researchers managed to reactivate ferroptosis in MM cells, making them more susceptible to destruction. In mouse models, oral administration of the inhibitor triggered ferroptosis, increased iron uptake by the cancer cells, and resulted in significant tumor reduction.
These findings suggest that STK17B acts as a protective safeguard for MM cells against iron toxicity. Blocking it could be a promising therapeutic approach, potentially overcoming resistance to current treatments. The team has filed a provisional patent and aims to further develop and optimize this therapy, with plans to explore its application in other cancers resistant to ferroptosis.
Nikiforov emphasizes the broader implications: "Many other cancer types also resist ferroptosis. Our hope is that this inhibitor could improve treatment outcomes across a range of tumors, providing a new pathway to combat drug resistance and improve long-term survival." Source: https://medicalxpress.com/news/2025-09-iron-destroy-multiple-myeloma-cancer.html
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