TY - JOUR
T1 - Targeted CML therapy
T2 - Controlling drug resistance, seeking cure
AU - O'Hare, Thomas
AU - Corbin, Amie S.
AU - Druker, Brian J.
N1 - Funding Information:
We thank Christopher A Eide for figure preparation, and our colleagues in the Druker laboratory for valuable input. BJD is supported by grants from the National Cancer Institute, The Leukemia and Lymphoma Society, the Burroughs Wellcome Foundation, and by the Howard Hughes Medical Institute.
PY - 2006/2
Y1 - 2006/2
N2 - Targeted cancer therapy with imatinib (Gleevec) has the capability to drive chronic myeloid leukemia (CML) into clinical remission. Some patients, particularly those with advanced disease, develop resistance to imatinib. To counteract this problem, two new BCR-ABL kinase inhibitors for imatinib-refractory disease are currently in clinical trials: the imatinib derivative AMN107 and the dual-specificity SRC/ABL inhibitor dasatinib. Using imatinib to reduce leukemic burden also facilitates the detailed investigation into how the persistence of CML disease depends on BCR-ABL signaling, particularly within the leukemic stem cell compartment. Mathematical models of drug resistance and disease relapse, in addition to experimental systems that recapitulate crucial aspects of advanced disease have deepened our understanding of CML biology. Together, these advances are contributing to a high level of disease control, and might ultimately lead to disease eradication.
AB - Targeted cancer therapy with imatinib (Gleevec) has the capability to drive chronic myeloid leukemia (CML) into clinical remission. Some patients, particularly those with advanced disease, develop resistance to imatinib. To counteract this problem, two new BCR-ABL kinase inhibitors for imatinib-refractory disease are currently in clinical trials: the imatinib derivative AMN107 and the dual-specificity SRC/ABL inhibitor dasatinib. Using imatinib to reduce leukemic burden also facilitates the detailed investigation into how the persistence of CML disease depends on BCR-ABL signaling, particularly within the leukemic stem cell compartment. Mathematical models of drug resistance and disease relapse, in addition to experimental systems that recapitulate crucial aspects of advanced disease have deepened our understanding of CML biology. Together, these advances are contributing to a high level of disease control, and might ultimately lead to disease eradication.
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U2 - 10.1016/j.gde.2005.11.002
DO - 10.1016/j.gde.2005.11.002
M3 - Review article
C2 - 16343892
AN - SCOPUS:30644462841
SN - 0959-437X
VL - 16
SP - 92
EP - 99
JO - Current Opinion in Genetics and Development
JF - Current Opinion in Genetics and Development
IS - 1
ER -