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Chronic myelogenous leukemia (CML)

BCR-ABL tyrosine kinase

Cell culture studies suggest Bosulif bosutinib plus danusertib could help treat CML resistant to Gleevec imatinib. In primary cancer cells isolated from a patient with Gleevec-resistant CML, bosutinib and danusertib synergistically decreased cell proliferation compared with vehicle. The combination did not show a synergistic antiproliferative effect in cells from a patient with Gleevec-sensitive CML. Next steps could include testing the combination in a mouse model of Gleevec-resistant CML.
Novartis AG markets the BCR-ABL inhibitor Gleevec to treat CML and gastrointestinal stromal tumors (GISTs).
Pfizer Inc.'s Bosulif, a dual inhibitor of BCR-ABL and Src, is approved to treat CML.
Nerviano Medical Sciences s.r.l.'s aurora kinase inhibitor, danusertib (PHA-739358), is in Phase I and Phase II testing to treat various cancers.

SciBX 5(42); doi:10.1038/scibx.2012.1106
Published online Oct. 25, 2012

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Winter, G.E. et al. Nat. Chem. Biol.; published online Sept. 30, 2012;
Contact: Giulio Superti-Furga, Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria