TTK and neoplasm: By employing different pairs of tumor clones generated from the same parental cell lines and displaying distinct levels of ploidy (i.e., diploid vs. tetraploid) we provided strong evidence that the depletion or inhibition of MPS1 potently kills tetraploid cancer cells (and to a lesser extent diploid cancer cells) via a mechanism involving the induction of mitotic catastrophe following aberrant or aborted cell divisions, and the activation of a mitochondrion- and caspase-dependent pathway of regulated cell death.