In a recent study published in EMBO Molecular medicine, Zhang et al. provided a novel insight regarding better knowledge of the drug resistant contribution of drug-tolerant persister (DTP) state in tumor evolution, especially in terms of mechanistic insights into redox regulation involved, unambiguously establishing a novel therapeutic strategy of treating multi-drug-resistant (MDR) cancer cells and preventing tumor recurrence by disequilibrating Niemann–Pick C1-like 1 (NPC1L1)-mediated redox homeostasis.1 This evidence concerns the gene NPC1L1 and cancer.