Three weeks after i.v. injection of an equal number of spheroids per condition and mouse (approximately 750 spheroids), we observed much more extensive metastatic disease in the mice injected with spheroids containing macrophages with a locked NRF2-on state, irrespective of whether NRF2 was activated by heme or constitutively active as a result of the genetic absence of Keap1. The gene discussed is KEAP1; the disease is metastatic neoplasm.