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    Validating aurora b as an anticancer drug target

    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 .

    Auroras A and B are essential components of the mitotic pathway, ensuring proper chromosome assembly, formation of the mitotic spindle, and cytokinesis. Overexpression of aurora A and B has been observed in several tumor types, and has been linked with a poor prognosis of cancer patients.

    The Aurora family kinases contribute to accurate progression through several mitotic events.

    ZM447439 (“ZM”), the first Aurora family kinase inhibitor to be developed and characterized, was previously found to interfere with the mitotic spindle integrity checkpoint and chromosome segregation.

    Finally, under conditions where the spindle integrity checkpoint was experimentally induced, ZM blocked the establishment, but not the maintenance, of the checkpoint, at a point upstream of the checkpoint protein Mad2.

    These results show that Aurora kinase activity is required to ensure the maintenance of condensed chromosomes, the generation of chromosome-induced spindle microtubules, and activation of the spindle integrity checkpoint.

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