KRAS and colorectal carcinoma: KRAS mutation is considered a negative prognostic marker in metastatic CRC.28 Hence, we believe that the worse survival observed in patients with RAS mutations in our study is probably associated with the negative prognostic impact of this alteration and not with a predictive value of response to the combination of metformin and irinotecan; the absence of a control arm in our study, however, prevents us from reaching a definitive conclusion.