Cell-state-specific metabolic networks govern ferroptosis versus apoptosis in small cell lung cancer.

A Cell study shows that all small cell lung cancer (SCLC) cell states depend on exogenous cysteine. Cells with low ASCL1 undergo ferroptosis upon cysteine depletion, while ASCL1-high cells resist ferroptosis and undergo apoptosis through direct transcriptional activation of GCH1, raising BH4/BH2. Combining cysteine depletion with BH4 synthesis inhibition suppressed tumor growth in patient-derived xenograft models (DOI: 10.1016/j.cell.2026.09.045).