Preclinical and clinical experience with dasatinib in Philadelphia chromosome-negative leukemias and myeloid disorders.
Recent advances in the molecular characterization of Philadelphia chromosome-negative (Ph-) leukemias and related myeloid disorders have provided a clear rationale for investigating novel targeted therapies. Dasatinib is a tyrosine kinase inhibitor with activity against BCR-ABL, platelet-derived growth factor receptors (PDGFRs), c- KIT, fibroblast growth factor receptors (FGFRs), SRC family kinases (SFKs), and EPHA receptors, all of which have been implicated in the pathogenesis of Ph- leukemias and myeloid disorders. This review presents emerging data on the preclinical and clinical activity of dasatinib in these diseases, which suggest that larger clinical studies are warranted.
Verstovsek
Srdan
S
Leukemia Department, M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 428, Houston, TX 77030, USA. sverstov@mdanderson.org
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000069439:Dasatinib; D006801:Humans; D054438:Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / Q000188:drug therapy* / Q000235:genetics; D011743:Pyrimidines / Q000627:therapeutic use*; D013844:Thiazoles / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D011743:Pyrimidines; D013844:Thiazoles; D000069439:Dasatinib