Drug synergies for imatinib-resistant CML

Of the various imatinib-resistant mutations in chronic myeloid leukaemia (CML), BCR–ABL1^T315I has been particularly challenging to target using new inhibitors. Winter et al. screened combinations of inhibitors for synergistic cytotoxic effects on human and mouse BCR–ABL1^T315I-positive cells. They found that the pan-aurora kinase inhibitor danusertib synergized with the dual ABL1 and SRC inhibitor bosutinib. Proteomics and gene-expression analyses suggested that this synergism was due to cumulative off-target inhibition of multiple MAPK proteins, resulting in impaired MYC activity.