Because cancer therapies target live cells, quiescent cancer cells are a major roadblock to effective long-term treatment. Now, a team of scientists may have found the key to targeting quiescent cancer cells. Their findings were published yesterday in the journal Cell Reports.
The researchers from the University of Arizona and the University of Pittsburgh were able to find a way to manipulate a genetic “dimmer switch” for cell dormancy. This switch could potentially be used to make quiescence shallower so the cells do not hide from cancer therapies. Alternatively, it may also be used to make quiescence deeper so cells go so far into dormancy that they do not ever wake up.
The genetic switch operates within a group of genes called Retinoblastoma (Rb)-E2F, which had been previously found to play a pivotal role in cell division and cancer formation. The team created a computer model to simulate how changing the expression of different genes in the Rb-E2F network affected quiescence. The computer model predictions were tested using a rat-cell model to determine how easy it was to rouse sleeping cells after genetic manipulation.
This allowed the researchers to find multiple genes that altered quiescence to varying degrees. It was these genes that they used as a dimmer switch to fine tune the dormancy level in cells.
This finding reflects a continuation of extensive work done on the subject of quiescence in the lab of Guang Yao, Ph.D., UA assistant professor of molecular and cellular biology. He and his team plan to continue this research in the future, investigating how the Rb-E2F switch interacts with other quiescence regulatory pathways in other cell types and under different conditions.
Image: Cancer cells. Image courtesy of Cecil Fox, National Cancer Institute.