NFS1 deficiency enhances the antitumor effects of oxaliplatin via activation of multiple cell death pathways

Metabolic enzymes play an indispensable role in metabolic reprogramming, and their aberrant expression or activity is associated with the sensitivity to chemotherapy. Hence, targeting metabolic enzymes remains an attractive approach for treating tumors. Here, utilizing an in vivo metabolic enzyme gene-based clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 knockout library screen, we found that loss of cysteine desulfurase (NFS1), a rate-limiting enzyme in iron-sulfur (Fe-S) cluster biogenesis, was associated with the sensitivity of colorectal cancer (CRC) cells to oxaliplatin. High expression of NFS1, transcriptionally regulated by MYC, was revealed in tumor tissues and related to poor survival of CRC patients.