Consequences of mitotic slippage for antimicrotubule drug therapy

    1. Karen Crasta1,2,3,4
    1. 1Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
    2. 2School of Biological Sciences, Nanyang Technological University, Singapore, Singapore
    3. 3A*STAR Institute of Molecular and Cell Biology, Singapore, Singapore
    4. 4Department of Medicine, Imperial College London, London, UK
    1. Correspondence should be addressed to K Crasta; Email: kccrasta{at}ntu.edu.sg

    Abstract

    Antimicrotubule agents are commonly utilised as front-line therapies against several malignancies, either by themselves or as combination therapies. Cell-based studies have pinpointed the anti-proliferative basis of action to be a consequence of perturbation of microtubule dynamics leading to sustained activation of the spindle assembly checkpoint, prolonged mitotic arrest and mitotic cell death. However, depending on the biological context and cell type, cells may take an alternative route besides mitotic cell death via a process known as mitotic slippage. Here, mitotically arrested cells ‘slip’ to the next interphase without undergoing proper chromosome segregation and cytokinesis. These post-slippage cells in turn have two main cell fates, either cell death or a G1 arrest ensuing in senescence. In this review, we take a look at the factors determining mitotic cell death vs mitotic slippage, post-slippage cell fates and accompanying features, and their consequences for antimicrotubule drug treatment outcomes.

    Keywords
    • Received 4 July 2017
    • Accepted 6 July 2017
    • Made available online as an Accepted Preprint 6 July 2017
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