Dasatinib is an orally available multikinase inhibitor indicated for the treatment of Philadelphia chromosome (Ph)-positive leukemias. Ph is a chromosomal abnormality found in patients with chronic myelogenous leukemia (CML) and acute lymphocytic leukemia (ALL), where the ABL tyrosine kinase and the breakpoint cluster region (BCR) gene transcribe the chimeric protein BCR-ABL. BCR-ABL is associated with the uncontrolled activity of the ABL tyrosine kinase and is involved in the pathogenesis of CML and 15-30% of ALL cases. Dasatinib also inhibits a spectrum of kinases involved in cancer, including several SRC-family kinases.
Unlike imatinib, another tyrosine kinase used for the treatment of CML and Ph-positive ALL, dasatinib inhibits the active and inactive conformations of the ABL kinase domain. Also, mutations in the kinase domain of BCR-ABL may lead to relapse during imatinib treatment. Since dasatinib does not interact with some of the residues involved in those mutations, the use of this drug represents a therapeutic alternative for patients with cancers that have developed imatinib-resistance. The use of dasatinib was first approved by the FDA in 2006.
Dasatinib is indicated for the treatment of newly diagnosed adults with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase, as well as adults with chronic, accelerated, or myeloid or lymphoid blast phase Ph+ CML with resistance or intolerance to prior therapy including imatinib, and adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with resistance or intolerance to prior therapy. Dasatinib is also indicated for the treatment of pediatric patients 1 year of age and older with Ph+ CML in chronic phase or newly diagnosed Ph+ ALL in combination with chemotherapy.
Barbara Ann Karmanos Cancer Institute, Detroit, Michigan, United States
Memorial Sloan-Kettering Cancer Center, New York, New York, United States
VUMedical Center, Amsterdam, Netherlands
Nippon Medical School, Sendagi 1-1-5, Bunkyo-ku,Tokyo, Japan
OHSU Knight Cancer Institute, Portland, Oregon, United States
Barbara Ann Karmanos Cancer Institute, Detroit, Michigan, United States
Northern Indiana Cancer Research Consortium, Crown Point, Indiana, United States
Local Institution - 0006, Fontana, California, United States
Local Institution - 0021, Roma, Italy
H. Lee Moffitt Cancer & Research Institute, Tampa, Florida, United States
The Ottawa Hospital Cancer Centre, Ottawa, Ontario, Canada
Local Institution, Gwent, United Kingdom
University of Texas MD Anderson Cancer Center, Houston, Texas, United States
Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States
Massachusetts General Hospital, Boston, Massachusetts, United States
Dana-Farber Cancer Institute, Boston, Massachusetts, United States
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