dasatinib + cyclosporine

dasatinib + cyclosporine is a combination therapy evaluated for the treatment of Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML). Dasatinib is a second-generation tyrosine kinase inhibitor (TKI) that targets BCR-ABL and Src family kinases, which are critical for the survival and proliferation of leukemic cells. Cyclosporine, a calcineurin inhibitor and immunosuppressant, is used in this context as a chemosensitizer. It is hypothesized to inhibit the P-glycoprotein (P-gp/ABCB1) efflux pump, which often mediates resistance to TKIs by pumping the drug out of the cell. By inhibiting P-gp, cyclosporine increases the intracellular concentration of dasatinib, potentially overcoming resistance in patients who are refractory or intolerant to imatinib. This regimen was the focus of the NCI-sponsored Phase Ib trial ESCAPE1b.

Brand names

SprycelSandimmuneNeoralGengraf

Other names

Dasatinib and Cyclosporine