Small molecules are attractive agents for the treatment of leukemia. We found that a combination of a farnesyltransferase inhibitor, tipifarnib, and an mTOR inhibitor, rapamycin, synergistically inhibited the growth of myeloid leukemia cell lines and primary leukemia cells by inducing apoptosis and cell-cycle blockage. The combined agents reduced the level of phospho-ERK1/2, suggesting that they altered the network of signaling pathways. They also showed synergistic effects in tipifarnib-resistant K562/RR cells. The results support the utility of this combination as a potential therapy for leukemia. The combination might also be effective in overcoming resistance to tipifarnib.
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