Cancer cells adopt unprecedented strategies to produce a molecule that protects them from iron-dependent death

Cancer cells have developed novel mechanisms to produce spermine, a molecule that shields them from ferroptosis, a form of iron-dependent cell death. This discovery, published in Nature on June 22, 2026, reveals that cancer cells upregulate the expression of genes involved in spermine synthesis, including ODC1 and SMOX. These cells exhibit significantly higher levels of spermine compared to healthy cells, which researchers observed through transcriptomic and proteomic analyses. The increased spermine concentration effectively chelates intracellular iron, preventing the oxidative damage that triggers ferroptosis. This protective strategy allows cancer cells to survive and proliferate even in environments with high iron availability. The study, led by researchers at the Karolinska Institute, utilized CRISPR-Cas9 gene editing to demonstrate that inhibiting spermine production in cancer cells renders them susceptible to ferroptosis. This finding has significant implications for cancer therapy, suggesting that targeting spermine synthesis could be a viable approach to induce cancer cell death. Furthermore, understanding this mechanism may also offer new avenues for treating conditions involving tissue damage where ferroptosis plays a detrimental role.