To evaluate whether targeting MTHFD2 was responsible for the observed toxicity on MTHFD2 inhibitors in cancer cells, we generated MTHFD2−/− clustered regularly interspaced short palindromic repeats (CRISPR)–Cas9 knockout cells and found that they were several orders of magnitude more resistant to TH9619 than parental MTHFD2 WT cells (Fig. 2e), but not MTHFD1−/− cells (Extended Data Fig. 2). Here, MTHFD2 is linked to cancer.