KEAP1 and cancer: In particular, oncogenic mutations in upstream pathway genes—such as activating mutations in an oncogene or inactivating mutations in a tumor suppressor—are associated with increased dependencies on genes that are downstream in the same pathway and that promote cancer; e.g., NFE2L2 dependency in cell lines with inactivating mutations in KEAP1 and MAPK1 dependency in cell lines with activating mutations in BRAF. These results are consistent with the notion that cancer cells develop addiction to an oncogenic pathway during cancer progression.21