BRAF mutations suggest that patients are unlikely to benefit from anti-EGFR treatments,76 and this mutation has become the basis for the development of new treatment strategies, such as targeted therapy for BRAF V600E.77 Unlike BRAF, alterations in SMAD4 more reflect the invasiveness and metastatic potential of the tumor, rather than being a direct predictor of response. The gene discussed is SMAD4; the disease is neoplasm.