Lupini et al [47] evaluated response of CRC to anti-EGFR antibody-based therapy in patients with different mutations (including KRAS, NRAS, BRAF, PI3KCA, and SMAD4 mutations) and found a higher number of nonresponders in the SMAD4-mutated arm, although the difference between the 2 treatment arms based on mutational status was not statistically significant (possibly owing to small numbers of patients: 4 versus 1). This evidence concerns the gene SMAD4 and colorectal carcinoma.