BAK1 and cancer: BEX2 inhibits mitochondrial apoptosis in breast tumors and plays a role in G1 cell cycle progression.53, 54 BEX2 also upregulates the pro-survival factor Bcl-2 and downregulates pro-apoptotic factors BAD, BAK1, and PUMA.53 Similarly, Bcl2A1 is an antiapoptotic protein that is highly expressed in many cancers.55 It has been implicated in tumorigenesis and chemoresistance,55 as well as resistance to the Bcl-2/Bcl-Xl inhibitor ABT-737.56 In the present study, ISRIB was well-tolerated in an orthotopic tumor model.