Checkpoint protein is key to cancer drugs

The operation of a built-in “security check” guarantees that cells divide with the correct number of chromosomes, a finding that could lead to the development of more effective cancer drugs. Most cells in the body contain 23 pairs of chromosomes that encode individual genetic identities. The process of chromosome segregation is monitored by a system called the spindle checkpoint that ensures daughter cells receive the correct number of chromosomes. If daughter cells receive an unequal number of chromosomes, known as “aneuploidy,” this drives normal cells to become cancerous. The cells of aggressive human tumors are frequently “aneuploid,”, with many components of the spindle checkpoint being mutated or misexpressed. Therefore, determining how the spindle checkpoint operates is vital to understanding what causes, and what can prevent, the formation of tumors. The new research published in the journal Current Biology pinpoints the precise mechanism by which spindle checkpoint proteins bind chromosomes. “Components of the spindle assembly checkpoint were first discovered 22 years ago by researchers in America and yet, until now, the binding sites for these proteins on chromosomes have remained unknown,” says Professor Jonathan Millar of the University of Warwick. “We have been able to answer this question and as a result, we are now in a much better position to design more selective and effective drugs.” Currently, one of the most frequently used anti-cancer drugs are taxanes, which prevent proper inactivation of the spindle checkpoint and result in selective death of cancer, but not normal cells. However, this class of drug can have debilitating side effects including permanent neurological damage and hair loss—side effects that could be reduced if cancer cells could be targeted more selectively. Millar is quick to point out that this is not an overnight cure. “This research is a significant advance in our understanding of how the spindle checkpoint operates but it is really just the start. More research has to be done before we can convert this into a commercial treatment for patients. But we are greatly encouraged that our research here at Warwick is leading the way in the search for more effective cancer drugs.”