Finally, three of the 23 EGFR-mutant NSCLCs harbored a concomitant mutation in either SMAD4, FGFR1, or FGFR3. The former encodes the SMAD4 transcriptional co-factor that mediates TGF-β tumor-suppressive function by inducing growth arrest and apoptosis [46], but the incidence and function of inactivating SMAD4-mutations in TKI-resistance are scantly known. Here, SMAD4 is linked to neoplasm.