Despite a study of the NSCLC genome showed a mutation rate of 4% among SMAD-genes [40], the incidence of inactivating SMAD4-mutations in EGFRM+ NSCLC has not been extensively studied and it remains poorly understood whether and how these mutations are implicated in intrinsic TKI-resistance. The gene discussed is SMAD4; the disease is non-small cell lung carcinoma.