Chromosome segregation errors: a double-edged sword - TI Pharma

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Abstract
Taxanes, such as docetaxel, are microtubule-targeting chemotherapeutics that have been successfully
used in the treatment of cancer. Based on data obtained from cell cultures, it is believed that taxanes
induce tumor cell death by specifically perturbing mitotic progression. However, recent studies
suggest that tumor cell death in vivo might not be caused by mitotic perturbations. Here we describe
a high-resolution intravital imaging method to simultaneously visualize mitotic progression and the
onset of apoptosis. To directly compare in vitro and in vivo data, we have visualized the effect of
docetaxel on mitotic progression in mouse and human colorectal tumor cell lines both in vitro and
in isogenic tumors in mice. We show that docetaxel-induced apoptosis in vitro occurs via mitotic cell
death, whereas tumor cells in their natural environment die independently of mitotic defects. Our
data demonstrate that docetaxel exerts its anti-tumor effects in vivo through means other than mitotic
perturbation.
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