Figure 7

Model for ABT-199-resistance and PI3K-mTOR-mediated targeting of ABT-199-R cells. (a) ABT-199 targets BCL-2 in sensitive cells and displaces BIM to cause apoptosis through BAX activation. (b) ABT-199 does not target MCL-1 and BCL-xL, which confers resistance by sequestering BIM displaced from BCL-2. (c) NVP-BEZ235 inhibits the PI3K and mTOR pathways, which interfere with MCL-1 stability, thereby freeing BIM, which then activates BAX, leading to release of cytochrome c to cause cell death