NFE2L2 and cancer: Interestingly, LGB-321 and AZD1208, two inhibitors of PIM kinase, a protein frequently overexpressed in many tumors exposed to hypoxia, were found to impair tumor growth and selectively kill different types of hypoxic cancer cells in vitro and in vivo, preventing NRF2 nuclear accumulation and leading to the buildup of ROS [328], suggesting that this strategy might overcome the hypoxia-mediated therapy resistance frequently encountered in the treatment of many tumors.