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Medline ® Abstract for Reference 6

of 'Clinical use of tyrosine kinase inhibitors for chronic myeloid leukemia'

Second generation inhibitors of BCR-ABL for the treatment of imatinib-resistant chronic myeloid leukaemia.
Weisberg E, Manley PW, Cowan-Jacob SW, Hochhaus A, Griffin JD
Nat Rev Cancer. 2007;7(5):345.
Imatinib, a small-molecule ABL kinase inhibitor, is a highly effective therapy for early-phase chronic myeloid leukaemia (CML), which has constitutively active ABL kinase activity owing to the expression of the BCR-ABL fusion protein. However, there is a high relapse rate among advanced- and blast-crisis-phase patients owing to the development of mutations in the ABL kinase domain that cause drug resistance. Several second-generation ABL kinase inhibitors have been or are being developed for the treatment of imatinib-resistant CML. Here, we describe the mechanism of action of imatinib in CML, the structural basis of imatinib resistance, and the potential of second-generation BCR-ABL inhibitors to circumvent resistance.
Dana Farber Cancer Institute, Mayer 540, 44 Binney Street, Boston, MA 02115, USA.