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.
Local Institution, Lodz, Poland
Local Institution - 0006, Krakรณw, Maลopolskie, Poland
Local Institution - 0002, Wroclaw, Poland
McGill University Health Centre, Montreal, Quebec, Canada
Hopital Maisonneuve-Rosemont, Montreal, Quebec, Canada
Juravinski Cancer Centre, Hamilton, Ontario, Canada
Gustave Roussy, Villejuif, Val De Marne, France
Springfield Memorial Hospital, Springfield, Illinois, United States
University of Arizona Cancer Center-North Campus, Tucson, Arizona, United States
John L McClellan Memorial Veterans Hospital, Little Rock, Arkansas, United States
University Hospital, Angers, France
Memorial Sloan Kettering Cancer Center Memorial Sloan Kettering, New York, New York, United States
Novartis Investigative Site, Madrid, Spain
Dana Farber Cancer Institute Hematology / Oncology, Boston, Massachusetts, United States
Illinois CancerCare-Princeton, Princeton, Illinois, United States
Aurora Cancer Care-Kenosha South, Kenosha, Wisconsin, United States
Columbus Oncology and Hematology Associates Inc, Columbus, Ohio, United States
UCSD, Division of Blood and Marrow Transplantation, Moores Cancer Center, La Jolla, California, United States
Hematological Malignancies/Stem Cell Transplantation Unit, David Geffen School of Medicine at UCLA, Los Angeles, California, United States
University of California Davis Comprehensive Cancer Center, Sacramento, California, United States
Seattle Children's, Seattle, Washington, United States
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