Molecular basis of drug resistance in aurora kinases.

  title={Molecular basis of drug resistance in aurora kinases.},
  author={Fiona Girdler and Fabio Sessa and Simona Patercoli and Fabrizio Villa and Andrea Musacchio and Stephen Taylor},
  journal={Chemistry & biology},
  volume={15 6},
Aurora kinases have emerged as potential targets in cancer therapy, and several drugs are currently undergoing preclinical and clinical validation. Whether clinical resistance to these drugs can arise is unclear. We exploited a hypermutagenic cancer cell line to select mutations conferring resistance to a well-studied Aurora inhibitor, ZM447439. All resistant clones contained dominant point mutations in Aurora B. Three mutations map to residues in the ATP-binding pocket that are distinct from… CONTINUE READING

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