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Recurrence and treatment resistance are major causes of cancer-associated death. There has been a growing interest in better understanding epithelial-mesenchymal transition (EMT), stemness of cancer cells, and exhaustion and dysfunction of the immune system for which numerous genomic, proteomic, microenvironmental, and immunological mechanisms have been demonstrated. However, practical treatments for such patients have not yet been established. Here we identified interleukin-33 (IL33) as a key driver of polyploidy followed by rapid pro