ERN1 and cancer: Consistently, blocking IRE1α by MKC8866 in PCa, BCa, and pancreatic cancer mouse models led to synergistic effects with the clinically approved anti-cancer drugs, such as enzalutamide, abiraterone, cabazitaxel, docetaxel, sotarasib, and trametinib, all of which are known to eventually lose efficacy in the clinic due to development of resistance [81, 83, 84, 96].