Wang et al. found that Dextromethorphan and Metformin, at their pharmacological doses, could synergistically repress nicotine-enhanced cancer-initiating cell properties and halt tumor progression by directly targeting CHRNA7 to inhibit JAK2/STAT3/SOX2 signaling in esophageal squamous cell carcinoma and perhaps other nicotine-sensitive cancer types (Wang et al., 2021a). Here, SOX2 is linked to esophageal squamous cell carcinoma.