Cancer cells display profound intra- and interline variation following prolonged exposure to antimitotic drugs (Cancer Cell, 2008, 14:111-122)

報告日期: 2008/11/21
報告時間: 16:00/16:50
報告學生: 許哲裕
講評老師: 賴明德

Cancer Cells Display Profound Intra- and Interline Variation following Prolonged Exposure to Antimitotic Drugs


Karen E. Gascoigne and Stephen S. Taylor


Cancer Cell. 2008 Aug 12;14(2):111-22

Speaker: 許哲裕

Commentator: 賴明德 老師

Date: Nov. 21, 2008. 16:00-16:50

Place: 602R



Drugs targeting the mitotic spindle are used extensively during chemotherapy, but surprisingly, little is known about how they kill tumor cells. This is largely because many of the population-based approaches are indirect and lead to vague and confusing interpretations. In addition to killing tumor cells, these cytotoxins affect normal dividing cells, causing myelosuppression, and nondividing cells, causing the peripheral neuropathies. To minimize neurotoxicity, new agents are being developed that disrupt mitosis without affecting microtubules. Front-runners include Eg5 kinesin inhibitors and inhibitors of mitotic kinases. Whether these new agents will exert significant antitumor effects is currently under investigation.

Until now, we still have little understanding of the mechanisms that dictate cell fate in response to either traditional antimitotic drugs or these new agents. Here, authors take a systematic, single-cell-based approach to describe how different tumor cells respond to these drugs. They use a high-throughput automated time-lapse light microscopy approach to analyze over 10,000 single cells from 15 cell lines in response to three different classes of antimitotic drug. They show that the variation in cell behavior is far greater than previously recognized, with cells within any given lines exhibiting multiple fates. Finally, they present data supporting a model wherein cell fate is dictated by two competing networks, one involving caspase activation, the other protecting cyclin B1 from degradation.



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