Mechanisms of resistance to FGFR1 inhibitors in FGFR1-driven leukemias and lymphomas: implications for optimized treatment

have been recognized as leading to resistance and both operate through the PI3K/AKT signaling axis. One of the important consequences is the suppression of PUMA, a potent enforcer of apoptosis, which operates through BCL2. Targeting BCL2 in the resistant cells leads to suppression of leukemia development in mouse models, which potentially provides an opportunity to treat patients that become resistant to FGFR1 inhibitors. In addition, elucidation of molecular mechanisms underlying FGFR1-driven leukemias and lymphomas also provides new targets for combined treatment as another option to bypass the FGFR1 inhibitor resistance and improve patient outcome.