The transcriptional regulator Sox2 has been shown to be directly regulated in developmental and cancer contexts by Six1 (Zhang T. et al., 2017; De Lope et al., 2019), Six2 (Cheng et al., 2019; Oliphant et al., 2019), Six3 (Liu et al., 2006), and Six6 (Diacou et al., 2018) to further promote stem/progenitor cell phenotypes. The gene discussed is SIX2; the disease is cancer.