Biopsies from up to 14% of patients with non-small-cell lung cancer (NSCLC) showing resistance to epidermal growth factor receptor (EGFR) tyrosine kinase therapy ascertain histologic transformation (HT) to SCLC, which is estimated to kill around 250,000 patients globally, every year. In a study published in Science on Feb. 9, 2024, researchers from Weill Cornell Medicine have dissected that complex process using a genetically engineered mouse model of pulmonary HT.