Researchers used CRISPR genome editing in mice models to reveal that different EML4-ALK gene fusion variants in lung adenocarcinoma drive distinct tumor growth kinetics and responses to treatment. Variant 3 (V3) showed higher oncogenicity and drug resistance compared to V1. Further pharmacogenomic analysis demonstrated variant-specific tumor suppressor gene interactions, emphasizing the need for subtype-specific therapies in ALK-positive lung cancer patients.