Overview

• Tuft-like tumors associated with poor outcomes arose only when cancer-driving changes were introduced into basal cells, not neuroendocrine cells.
• The study combined genetically engineered mice, 3D tumor organoids, lineage barcoding and analysis of the largest available human SCLC dataset.
• Results show SCLC cells can switch identities through cell fate plasticity, offering an explanation for treatment resistance.
• Researchers developed the first accurate lab models of tuft-like SCLC to enable studies of early detection, immune interactions and prevention-oriented therapies.
• SCLC accounts for 10–15% of lung cancers in the U.S., with about 30,000 diagnoses annually and a five-year survival rate under 10%.