In the present study, we were able to rescue long-term survival of U2OS cancer cells on MTHFD2 small interfering (si)RNA treatment by reintroducing wild-type (WT) siRNA-resistant MTHFD2, but not the siRNA-resistant, catalytically dead construct (Gln132Lys/Asp155Ala) carrying point mutations in the tetrahyrofolate (THF)-binding pocket (Fig. 1a). This evidence concerns the gene MTHFD2 and cancer.