Figure 1. The impact of carfilzomib and oprozomib on HNSCC cells. Treatment of HNSCC cells with carfilzomib or oprozomib leads to induction of BIK, which mediates apoptosis induction. Carfilzomib and oprozomib also induce MCL1, which attenuates apoptosis by these compounds. Inhibition of the proteasome by carfilzomib and oprozomib also leads to activation of the unfolded protein response, resulting in upregulation of ATF4. Induction of ATF4 stimulates autophagy in HNSCC cells, which acts to promote cell survival.