Characterized resistance mechanisms to osimertinib, the current standard of care, include amplifications of cell cycle genes CCND1 and CDK4 [22,23]; amplification of the receptor tyrosine kinases MET [23,24,25] and HER2 [23]; acquired oncogenic fusions in ALK [26], RET [24,27], ROS1 [28], and NTRK1 [23]; mutations in BRAF [23], KRAS [23,25], and PI3K [23,24,25]; loss of PTEN [29]; acquired secondary/tertiary EGFR mutations [23,24,25]; and phenotypic transformation to small cell lung cancer [30,31], all of which have been validated as acquired resistance mechanisms in pre-clinical models. Here, NTRK1 is linked to small cell lung carcinoma.