FIGURE 3.

Manipulation of ISR in cancer therapy. ATF4 induction can be achieved either through kinase activators such as bortezomib, gemcitabline, lopinavir, CCT020312, halofuginone, arginine deiminase, STAT3 inhibitors, BEPP, BTdCPU and ONC201 or the inhibitors of phosphatases such as salubrinal, guanabenz and nelfinavir. In the case of ISR promotes cancer cell survival and resistant to therapeutic treatments, inhibition of ATF4 can be achieved by kinase inhibitors such as LY-4, GSK2606414, AMG-44, BCR-ABL inhibitors, SP600125, C16 and aminopyranzolindane or compound ISRIB downstream of eIF2α phosphorylation.