| Abstract: | BCR-ABL, a constitutively active tyrosine kinase, causes chronic myeloid leukaemia (CML). Rational development of drugs targeting BCR-ABL has significantly improved the treatment of CML. Imatinib (a BCR-ABL tyrosine kinase inhibitor) produces haematological and cytogenetic remissions across all phases of CML and is the present standard of care. Imatinib resistance occurs in a significant proportion of patients and mechanisms of resistance include BCR-ABL mutations and activation of alternate oncogenic pathways. Dasatinib is a novel, potent, multi-targeted oral kinase inhibitor. Preclinical and clinical investigations demonstrate that dasatinib effectively overcomes imatinib resistance and has further improved the treatment of CML. Dasatinib was recently approved by the FDA for use in Philadelphia-positive leukaemias in patients who are resistant or intolerant to imatinib. |
