Finally, the use of therapeutically effective but relatively high doses of FDA-approved proteasome inhibitors for cancer therapy can induce drug resistance,73 in which cancer cells trigger an adaptive response to overcome these inhibitors by enhancing Nrf1/2-driven proteasome gene transcription.74, 75 We suggest that this can be circumvented without reduction in therapeutic efficacy by combining lower dose Bortezomib with co-targeting of CK1α, an emerging key effector of RAS-mutant cancer cell survival. The gene discussed is CSNK1A1; the disease is cancer.