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CHRISTOPHER A. FAUSEL, PHARM.D., BCPS, BCOP, is Clinical Pharmacist, Hematology/Oncology/Bone Marrow Transplant, Indiana University Cancer Center, 535 Barnhill Drive, Indianapolis, IN 46202 (cfausel{at}clarian.org).

Purpose. Despite dramatic advances in the treatment of chronic myeloid leukemia (CML), resistance to therapeutic agents has emerged as a significant treatment dilemma. Mutations of the BCR-ABL kinase domain, a common mechanism of resistance to imatinib in CML, are discussed. Summary. Several new targeted kinase inhibitors have reached clinical trials and have proved to be efficacious in halting the oncogenic activity of most BCR-ABL mutants. Dasatinib is 300 times more potent than imatinib at BCR-ABL inhibition, has few side effects, and inhibits the SRC family kinases. Nilotinib inhibits BCR-ABL at 20–50 times more potency than imatinib. Both agents were highly effective in treating chronic phase CML but were less effective at treating accelerated phase CML in early phase clinical trials. In addition to these specific kinase inhibitors, farnesyl transferase inhibitors are actively being investigated. Vaccination strategies are undergoing clinical investigation transitioning from animal models to human clinical trials. Conclusion. The new kinase inhibitors, dasatinib and nilotinib, are emerging as plausible therapeutic options for the treatment of imatinib-refractory CML. Index terms: Antineoplastic agents; Dasatinib; Drug comparisons; Farnesyl transferase inhibitors; Imatinib; Leukemia; Mechanism of action; Neoplasm vaccines; Nilotinib; Research; Resistance; Site of action; Toxicity; Vaccines