GCLM and cancer: Some cancer cells can survive via a set of defense mechanisms, such as the upregulation of antioxidant enzymes and the modification of sulfur-based metabolism, during chemotherapy treatment, and these mechanisms enable the cells to become hyposensitive and even resistant to many chemotherapeutic drugs.10,35,41 Many inhibitors targeting antioxidant enzymes, such as GSS, GCLC, GCLM, GPX, TXNRD, and CAT, are undergoing clinical trials for the treatment of certain drug-resistant cancers.33 We also found that NFS1 expression was positively correlated with these antioxidant enzymes.