Escape from mitotic arrest; compounds that induce mitotic slippage as tools for chemical biology and potential therapeutic agents

One of the main characteristics of cancer is the uncontrolled division and growth of cells. Because tumour cells divide very frequently, tumour growth can be selectively stopped by inhibiting cell division. Commonly-used cancer drugs act by effectively “freezing” cell activity right in the process of division. This is done by interfering with mitosis – the point in the cell cycle where the nuclear chromosomes have been duplicated and separated to form two daughter cells. Unlike normal cells, some cancer cells eventually bypass this frozen state in a process known as mitotic slippage. However, the resulting cells now contain too many sets of chromosomes. Researchers still don’t know what happens to these drug-treated cancer cells as a result of mitotic slippage – whether they are able to start dividing again, whether they remain in an arrested state indefinitely, or whether they die. Jenna Riffell is investigating the fate of cancer cells after drug treatment. She is identifying chemical compounds that can stimulate drug-treated cancer cells to undergo mitotic slippage, and monitoring what happens to these cells. Her hypothesis is that the rate of mitotic slippage can be increased with chemicals, and will prompt growth arrest or cell death. If proven successful, this approach could be used for the development of future cancer therapies. In addition, Riffell’s work will be useful for studying the underlying biochemical mechanisms of cell division.