Antimitotic Drugs Trigger Race for Survival in Cancer Cells

Cancer researchers have discovered new insights into how antimitotic chemotherapeutic agents work and hope to translate this knowledge into a new generation of drugs with much reduced toxic side effects.

Investigators at the University of Manchester (UK) took advantage of a newly acquired, fully automated microscope to watch cancer cells using time-lapse microscopy, which allowed them to track the behavior of individual cells and determine their fate when exposed to different anti-mitotic drugs.

Eventually, the study grew to include more than 10,000 single cells from 15 cell lines in response to three different classes of antimitotic drugs. Results that were published in the August 2008, issue of the journal Cancer Cell revealed that the variation in cell behavior was far greater than previously recognized, with cells within any given line exhibiting multiple fates. Simply put, when faced with an antimitotic drug, a cancer cell could either die (the best result as far as a patient is concerned) or remain in stasis until the drug went away.

"We embarked on a fresh, more direct approach that is actually quite simple,” said senior author Dr. Stephen Taylor, professor of life sciences at the University of Manchester. "Basically, we just watched the cells using time-lapse microscopy; this allowed us to track the behavior of individual cells and determine their fate when exposed to different antimitotic drugs. In essence, it turns out that when cells are exposed to these drugs they arrest in mitosis. Then a race starts between two competing cellular signaling networks. One network is trying to kill the cell, the other is trying to cause the cell to exit mitosis and thus allow the cell to survive. The winner of the race decides the fate of the cell: death or survival. The factors influencing the race not only vary from cell line to cell line, but also within cells from the same line, explaining why there is so much complexity. What we want to do now is figure out how we can help the cell death pathway win the race more often; this would hopefully mean that the antimitotic drugs would be better at killing cancer cells. First we want to test this idea in the lab but hopefully in the longer run this will mean that these drugs can be used more effectively in the clinic.”

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