For instance, the treatment of 5-FU decreases the expression of serine hydroxymethyltransferase-2 (SHMT2), which promotes autophagy and triggers 5-FU resistance, resulting in poor prognosis of CRC patients; while 5-FU combined with the autophagy inhibitor chloroquine (CQ) reverses the insensitivity to 5-FU in CRC cells with low SHMT2 expression in vitro and in vivo, thereby enhancing the effect of chemotherapy (59). This evidence concerns the gene SHMT2 and colorectal carcinoma.