To overcome the drug resistance arising from NTRK mutations, such as the NTRK3 solvent front mutation G623R [35], second-generation inhibitors are under development or in clinical trials [8] In this study, we demonstrate the importance of the BTB domain of the N-terminal fusion partner NACC2 as a potential drug target that could be utilized to overcome drug resistance in patients with NACC2-NTRK2-driven cancers. This evidence concerns the gene NACC2 and cancer.