ROS1 and non-small cell lung carcinoma: In conclusion, this study aims to refine the pre-clinical ROS1 + NSCLC models by knocking-in resistance mutations G2032R, L2026M and S1986Y via CRISPR/Cas9 in the ROS1 + patient-derived HCC78 cell line, followed by functional characterization and pharmacological assays in 2D and 3D cultures.