Targeting Cystine Addiction Suppresses Breast Cancer Lung Metastasis.

Targeting cystine/cysteine metabolism with cyst(e)inase reduces lung metastasis in MYC-driven breast cancer models by exploiting a metabolic vulnerability of metastatic cells.

• Why it matters: Metastatic disease is a leading cause of cancer-related death, and understanding the unique metabolic features of metastasizing cells could enable more effective therapies.
• What they did: Using in vivo and ex vivo models, the study employed metabolomics, mass spectrometry imaging, and single-cell RNA sequencing to show that lung metastases depend on increased cystine uptake and glutathione synthesis, especially due to downregulated intracellular cysteine synthesis.
• The result: Combining cyst(e)inase with radiotherapy significantly decreased metastatic burden, suggesting that targeting cystine/cysteine metabolism can sensitize metastatic cells to oxidative stress and improve treatment outcomes.