Systems-pharmacology dissection of a drug synergy in imatinib-resistant CML.

  title={Systems-pharmacology dissection of a drug synergy in imatinib-resistant CML.},
  author={Georg E Winter and Uwe Rix and Scott M. Carlson and Karoline V. Gleixner and Florian Grebien and Manuela Gridling and Andr{\'e} C. Mueller and Florian P. Breitwieser and Martin Bilban and Jacques Colinge and Peter Valent and Keiryn L. Bennett and Forest M. White and Giulio Superti-Furga},
  journal={Nature chemical biology},
  volume={8 11},
Occurrence of the BCR-ABL(T315I) gatekeeper mutation is among the most pressing challenges in the therapy of chronic myeloid leukemia (CML). Several BCR-ABL inhibitors have multiple targets and pleiotropic effects that could be exploited for their synergistic potential. Testing combinations of such kinase inhibitors identified a strong synergy between danusertib and bosutinib that exclusively affected CML cells harboring BCR-ABL(T315I). To elucidate the underlying mechanisms, we applied a… CONTINUE READING


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