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Aberrant cell proliferation induced by activated oncogenes triggers oxidative stress and uncontrolled DNA replication, promoting genomic instability. We recently reported that human mammary stem cells exhibit the unique capacity to withstand an oncogenic activation by dint of an anti-oxidant program driven by the ZEB1 transcription factor. This pre-emptive program prevents the onset of chromosomal instability, leading to the development of tumors with unique pathological features.