New Insights into Lung Cancer Origins and Lineage Plasticity

The study reveals that basal lung epithelial cells can give rise to diverse subtypes of small cell lung cancer (SCLC), including neuroendocrine and tuft-like states, with lineage plasticity driven by genetic factors like MYC and PTEN loss. Loss of ASCL1 promotes tuft-like POU2F3+ SCLC, and lineage tracing confirms transitions between subtypes, highlighting the role of cell of origin and genetic alterations in SCLC heterogeneity and plasticity.