The kinase ZAK serves as a molecular sensor of these collisions, initiating the ribotoxic stress response (RSR) and p38-mediated apoptosis.
ZAK expression increases as CML progresses from chronic phase to blast phase, where it sustains proliferation through AKT signaling but sensitizes cells to TKI-induced death.
Targeting the translational and metabolic machinery—including the mTOR-EEF2K axis and mitochondrial OXPHOS—presents new opportunities to overcome TKI resistance.
